Función de las proteínas microtubulares en neuronas



Jefe de línea/Investigador Principal: Jesús Avila de Grado,
Personal Científico: Félix Hernández Pérez, Carmen Laura Sayas Casanova,
Postdoctorales: Vega García Escudero, Diana Simón Sanz,
Becarios predoctorales: Almudena Fuster Matanzo, Jerónimo Jurado Arjona, Patricia Martín-Maestro Rojas,
Técnicos de investigación: Raquel Cuadros Catalán, Nuria De La Torre Alonso, Esther García García, Elena Langa Gabriel,



Resumen de investigación

Los objetivos que estamos desarrollando buscan:

a)Conocer la función de MAP1B (una proteína asociada a los microtúbulos) en la migración neuronal y en la navegación axonal.

b)Conocer el mecanismo de la formación de los agregados aberrantes de la proteína tau en procesos neurodegenerativos.

c)Reparar los daños causados por la ruptura axonal en neuronas maduras.

a) Nuestros resultados han indicado que, mientras en el ratón conteniendo MAP1B se produce la migración de los precursores neuronales a su localización específica. En el caso de los ratones que carecen de MAP1B la localización de los precursores neuronales es mucho más desordenada, existiendo un defecto en la organización laminar del neocortex. Estos experimentos han sido realizados en colaboración con el grupo del Dr. Eduardo Soriano. Finalmente, en colaboración con dicho grupo se ha observado que MAP1B interviene en procesos de navegación axonal regulados por netrina.

b)Nuestro trabajo ha continuado el estudio in vitro de la polimerización de la proteína asociada a los microtúbulos, tau. Las condiciones en las cuales tau modificado por fosforilación se ensambla con mayor eficiencia han sido descritas. Estas condiciones implican la presencia de quinonas como la coenzima Q, que en su forma oxidada facilita el ensamblaje de la proteína tau fosforilada. Estos experimentos in vitro han sido complementados con experimentos in vivo utilizando ratones transgénicos que sobreexpresan tau con alguna de las mutaciones que se encuentran en la demencia frontotemporal asociada al cromosoma 17 (FTDP-17), ratones que se han cruzado con otros transgénicos que sobreexpresaban la proteína APP mutada (mutación sueca). Los resultados obtenidos indican que la expresión del péptido amiloide facilita la fosforilación y ensamblaje de la proteína tau.

c)Finalmente, hemos continuado nuestros estudios sobre el uso de células de glia envolvente como reparadoras del daño axonal. Hemos aislado células inmortales que mantienen su capacidad para facilitar la extensión de axones dañados.

 

 



Publicaciones

 

[1]        Avila, J., Hermoso, J.M., Vinuela, E. and Salas, M. (1970). Subunit composition of B. subtilis RNA polymerase. Nature 226, 1244-5.

[2]        Avila, J., Hermoso, J.M., Vinuela, E. and Salas, M. (1971). Purification and properties of DNA-dependent RNA polymerase from Bacillus subtilis vegetative cells. Eur J Biochem 21, 526-35.

[3]        Hermoso, J.M., Avila, J., Jimenez, F. and Salas, M. (1972). RNA polymerase from Bacillus amyloliquefaciens. Biochim Biophys Acta 277, 280-3.

[4]        Chou, J.Y., Avila, J. and Martin, R.G. (1974). Viral DNA synthesis in cells infected by temperature-sensitive mutants of simian virus 40. J Virol 14, 116-24.

[5]        Jimenez, F., Avila, J., Vinuela, E. and Salas, M. (1974). Initiation of the transcription of phi29 DNA by Bacillus subtilis RNA polymerase. Biochim Biophys Acta 349, 320-7.

[6]        Martin, R.G., Chou, J.Y., Avila, J. and Saral, R. (1975). The semiautonomous replicon: a molecular model for the oncogenicity of SV40. Cold Spring Harb Symp Quant Biol 39 Pt 1, 17-24.

[7]        Avila, J., Saral, R., Martin, R.G. and Khoury, G. (1976). The temperature-sensitive defect in SV40 group D mutants. Virology 73, 89-95.

[8]        Corces, V.G. and Avila, J. (1978). Interaction of contractile proteins with DNA. Eur J Biochem 83, 529-35.

[9]        Corces, V.G., Salas, J., Salas, M.L. and Avila, J. (1978). Binding of microtubule proteins to DNA: specificity of the interaction. Eur J Biochem 86, 473-9.

[10]      Wiche, G., Corces, V.G. and Avila, J. (1978). Preferential binding of hog brain microtubule-associated proteins to mouse satellite versus bulk DNA preparations. Nature 273, 403-5.

[11]      Avila, J. (1980). DNA polymerase activity, probably DNA polymerase alpha, remains associated to microtubules after successive polymerization cycles. Biochem Biophys Res Commun 92, 237-46.

[12]      Corces, V.G., Manso, R., De La Torre, J., Avila, J., Nasr, A. and Wiche, G. (1980). Effects of DNA on microtubule assembly. Eur J Biochem 105, 7-16.

[13]      Manso-Martinez, R., Villasante, A. and Avila, J. (1980). Incorporation of the high-molecular-weight microtubule-associated protein 2 (MAP2) into microtubules at steady state in vitro. Eur J Biochem 105, 307-13.

[14]      Martin, R.G., Setlow, V.P., Chepelinsky, A.B., Seif, R., Lewis, A.M., Jr., Scher, C.D., Stiles, C.D. and Avila, J. (1980). Roles of the T antigens in transformation by SV40. Cold Spring Harb Symp Quant Biol 44 Pt 1, 311-24.

[15]      Villasante, A., de la Torre, J., Manso-Martinez, R. and Avila, J. (1980). Microtubule-associated-protein MAP1 is not implicated in the polymerization of microtubules. Eur J Biochem 112, 611-6.

[16]      Nieto, A., Avila, J. and Valdivia, M.M. (1981). Comparative measurement by radioimmunoassay of the brain microtubule-associated protein MAP2. Mol Cell Biochem 37, 185-9.

[17]      Villasante, A., Corces, V.G., Manso-Martinez, R. and Avila, J. (1981). Binding of microtubule protein to DNA and chromatin: possibility of simultaneous linkage of microtubule to nucleic and assembly of the microtubule structure. Nucleic Acids Res 9, 895-908.

[18]      Valdivia, M.M., Avila, J., Coll, J., Colaco, C. and Sandoval, I.V. (1982). Quantitation and characterization of the microtubule associated MAP2 in porcine tissues and its isolation from porcine (PK15) and human (HeLa) cell lines. Biochem Biophys Res Commun 105, 1241-9.

[19]      Avila, J., Montejo de Garcini, E., Wandosell, F., Villasante, A., Sogo, J.M. and Villanueva, N. (1983). Microtubule-associated protein MAP2 preferentially binds to a dA/dT sequence present in mouse satellite DNA. Embo J 2, 1229-34.

[20]      Esponda, P. and Avila, J. (1983). In vitro microtubule assembly on centrioles from mammalian spermatids. Eur J Cell Biol 30, 313-5.

[21]      Alcover, A., Molano, J., Renart, J., Gil-Aguado, A., Nieto, A. and Avila, J. (1984). Antibodies to vimentin intermediate filaments in sera from patients with systemic lupus erythematosus. Arthritis Rheum 27, 922-8.

[22]      Avila, J. (1984). Microtubule proteins from no neuronal cells. Hoppe-Seyler Zestschift für Physiologiste Chemie 365, 225-226.

[23]      Diez, J., Little, M. and Avila, J. (1984). Quantitative determination, isolation and characterization of pig lung tubulin. Biochem J 219, 277-85.

[24]      Serrano, L., Avila, J. and Maccioni, R.B. (1984). Controlled proteolysis of tubulin by subtilisin: localization of the site for MAP2 interaction. Biochemistry 23, 4675-81.

[25]      Serrano, L., Avila, J. and Maccioni, R.B. (1984). Limited proteolysis of tubulin and the localization of the binding site for colchicine. J Biol Chem 259, 6607-11.

[26]      Serrano, L., de la Torre, J., Maccioni, R.B. and Avila, J. (1984). Involvement of the carboxyl-terminal domain of tubulin in the regulation of its assembly. Proc Natl Acad Sci U S A 81, 5989-93.

[27]      Wandosell, F., Rodriguez-Campos, A., Fernandez Piqueras, J. and Avila, J. (1984). Identification of the microtubule-associated protein map2 and its binding sites on metaphase chromosomes from cultured cells. Chromosoma 90, 68-71.

[28]      Alcover, A., Hernandez, C. and Avila, J. (1985). Human vimentin autoantibodies preferentially interact with a peptide of 30kD mol. wt, located close to the amino-terminal of the molecule. Clin Exp Immunol 61, 24-30.

[29]      Alcover, A., Ramirez-Lafita, F., Hernandez, C., Nieto, A. and Avila, J. (1985). Antibodies to vimentin intermediate filaments in sera from patients with SLE and RA: quantitation by solid phase radioimmunoassay. J Rheumatol 12, 233-6.

[30]      del Mazo, J., Martín-Sempere and Avila, J. (1985). Cytological and biochemical characterization of the kinetochore in different cell types. Clinical Genetics 28, 426a.

[31]      Diez, J.C. and Avila, J. (1985). Homogeneity of lung tubulin isoforms during lung maturation. Biochimie 67, 1059-62.

[32]      Diez, J.C., de la Torre, J. and Avila, J. (1985). Differential association of the different brain microtubule proteins in different in vitro assembly conditions. Biochim Biophys Acta 838, 32-8.

[33]      Hargreaves, A.J. and Avila, J. (1985). Localization and characterization of tubulin-like proteins associated with brain mitochondria: the presence of a membrane-specific isoform. J Neurochem 45, 490-6.

[34]      Maccioni, R., Serrano, L. and Avila, J. (1985). Structural and functional domain of tubulin. Bio Essays 2, 165-169.

[35]      Ripoll, P., Pimpinelli, S., Valdivia, M.M. and Avila, J. (1985). A cell division mutant of Drosophila with a functionally abnormal spindle. Cell 41, 907-12.

[36]      Santisteban, P., Hargreaves, A.J., Cano, J., Avila, J. and Lamas, L. (1985). Effects of high doses of iodide on thyroid secretion: evidence for the presence of iodinated membrane tubulin. Endocrinology 117, 607-12.

[37]      Serrano, L. and Avila, J. (1985). The interaction between subunits in the tubulin dimer. Biochem J 230, 551-6.

[38]      Serrano, L., Montejo de Garcini, E., Hernandez, M.A. and Avila, J. (1985). Localization of the tubulin binding site for tau protein. Eur J Biochem 153, 595-600.

[39]      Wandosell, F. and Avila, J. (1985). Quantitative determination of tubulin and characterization of tubulin forms during development in Drosophila melanogaster. Cell Differ 16, 63-9.

[40]      Alcina, A., Hargreaves, A.J., Avila, J. and Fresno, M. (1986). A Trypanosoma cruzi monoclonal antibody that recognizes a superficial tubulin-like antigen. Biochem Biophys Res Commun 139, 1176-83.

[41]      de la Torre, J., Carrascosa, J.L. and Avila, J. (1986). The localization of tau proteins on the microtubule surface. Eur J Cell Biol 40, 233-7.

[42]      del Mazo, J., Martin-Sempere, M.J., Kremer, L. and Avila, J. (1986). Centromere pattern in different mouse seminiferous tubule cells. Cytogenet Cell Genet 43, 201-6.

[43]      Hargreaves, A.J., Montejo de Garcini, E. and Avila, J. (1986). The interaction between a Na+-channel toxin and brain microtubule proteins in vitro. Brain Res 387, 43-51.

[44]      Hargreaves, A.J., Wandosell, F. and Avila, J. (1986). Phosphorylation of tubulin enhances its interaction with membranes. Nature 323, 827-8.

[45]      Hernandez, M.A., Avila, J. and Andreu, J.M. (1986). Physicochemical characterization of the heat-stable microtubule-associated protein MAP2. Eur J Biochem 154, 41-8.

[46]      Maccioni, R.B., Serrano, L., Avila, J. and Cann, J.R. (1986). Characterization and structural aspects of the enhanced assembly of tubulin after removal of its carboxyl-terminal domain. Eur J Biochem 156, 375-81.

[47]      Montejo de Garcini, E., Diez, J.C. and Avila, J. (1986). Quantitation and characterization of tau factor in porcine tissues. Biochim Biophys Acta 881, 456-61.

[48]      Montejo de Garcini, E., Serrano, L. and Avila, J. (1986). Self assembly of microtubule associated protein tau into filaments resembling those found in Alzheimer disease. Biochem Biophys Res Commun 141, 790-6.

[49]      Serrano, L., de la Torre, J., Luduena, R.F. and Avila, J. (1986). The removal of the carboxy-terminal region of tubulin favors its vinblastine-induced aggregation into spiral-like structures. Arch Biochem Biophys 249, 611-5.

[50]      Serrano, L., Valencia, A., Caballero, R. and Avila, J. (1986). Localization of the high affinity calcium-binding site on tubulin molecule. J Biol Chem 261, 7076-81.

[51]      Serrano, L., Wandosell, F. and Avila, J. (1986). Location of the regions recognized by five commercial antibodies on the tubulin molecule. Anal Biochem 159, 253-9.

[52]      Serrano, L., Wandosell, F., de la Torre, J. and Avila, J. (1986). Proteolytic modification of tubulin. Methods Enzymol 134, 179-90.

[53]      Serrano, L., Wandosell, F., Diez, J.C. and Avila, J. (1986). The combined use of limited proteolysis and differential peptide staining for protein characterization. J Biochem Biophys Methods 12, 281-7.

[54]      Wandosell, F., Serrano, L. and Avila, J. (1986). A calcium binding protein from Drosophila melanogaster which activates cAMP phosphodiesterase: comparison of this protein with porcine brain calmodulin. Arch Biochem Biophys 247, 147-54.

[55]      Wandosell, F., Serrano, L., Hernandez, M.A. and Avila, J. (1986). Phosphorylation of tubulin by a calmodulin-dependent protein kinase. J Biol Chem 261, 10332-9.

[56]      del Mazo, J., Kremer, L. and Avila, J. (1987). Centromeric proteins recognized by CREST sera and meiotic chromosome segregation. Chromosoma 96, 55-9.

[57]      Diez, J.C., Avila, J., Nieto, J.M. and Andreu, J.M. (1987). Reversible inhibition of microtubules and cell growth by the bicyclic colchicine analogue MTC. Cell Motil Cytoskeleton 7, 178-86.

[58]      Hernandez, M.A., Wandosell, F. and Avila, J. (1987). Localization of the phosphorylation sites for different kinases in the microtubule-associated protein MAP2. J Neurochem 48, 84-93.

[59]      Montejo de Garcini, E. and Avila, J. (1987). In vitro conditions for the self-polymerization of the microtubule-associated protein, tau factor. J Biochem (Tokyo) 102, 1415-21.

[60]      Serrano, L., Diaz-Nido, J., Wandosell, F. and Avila, J. (1987). Tubulin phosphorylation by casein kinase II is similar to that found in vivo. J Cell Biol 105, 1731-9.

[61]      Wandosell, F. and Avila, J. (1987). Microtubule-associated proteins present in different developmental stages of Drosophila melanogaster. J Cell Biochem 35, 83-92.

[62]      Wandosell, F., Serrano, L. and Avila, J. (1987). Phosphorylation of alpha-tubulin carboxyl-terminal tyrosine prevents its incorporation into microtubules. J Biol Chem 262, 8268-73.

[63]      Alcina, A., Hargreaves, A.J., Avila, J., Hesketh, J.E. and Fresno, M. (1988). The detection of a spectrin-like protein in Trypanosoma cruzi with a polyclonal antibody. Cell Biol Int Rep 12, 979-85.

[64]      Avila, J., Serrano, L., Díaz-Nido, J., Wandosell, F. and Hernández, M.A. (1988). Regulation of the polymerization of tubulin. J. Muscle Cell Mot. Res. 9, 95.

[65]      Avila, J., Serrano, L., Hernández, M.A. and Díaz-Nido, J. (1988). Phosphorylation of neuronal microtubule proteins. Protoplasma 145, 82-88.

[66]      Correas, I. and Avila, J. (1988). Erythrocyte protein 4.1 associates with tubulin. Biochem J 255, 217-21.

[67]      Diaz-Nido, J., Serrano, L. and Avila, J. (1988). Differential phosphorylation of microtubule proteins by ATP and GTP. Mol Cell Biochem 79, 73-9.

[68]      Diaz-Nido, J., Serrano, L., Mendez, E. and Avila, J. (1988). A casein kinase II-related activity is involved in phosphorylation of microtubule-associated protein MAP-1B during neuroblastoma cell differentiation. J Cell Biol 106, 2057-65.

[69]      Hargreaves, A., Yusta, B., Aranda, A., Avila, J. and Pascual, A. (1988). Triiodothyronine (T3) induces neurite formation and increases synthesis of a protein related to MAP 1B in cultured cells of neuronal origin. Brain Res 466, 141-8.

[70]      Hernandez, M.A., Serrano, L. and Avila, J. (1988). Microtubule-associated protein, MAP2, is a calcium-binding protein. Biochim Biophys Acta 965, 195-201.

[71]      Kremer, L., Alvaro-Gracia, J.M., Ossorio, C. and Avila, J. (1988). Proteins responsible for anticentromere activity found in the sera of patients with CREST-associated Raynaud's phenomenon. Clin Exp Immunol 72, 465-9.

[72]      Kremer, L., del Mazo, J. and Avila, J. (1988). Identification of centromere proteins in different mammalian cells. Eur J Cell Biol 46, 196-9.

[73]      Kremer, L., Dominguez, J.E. and Avila, J. (1988). Detection of tubulin-binding proteins by an overlay assay. Anal Biochem 175, 91-5.

[74]      Montejo de Garcini, E., Carrascosa, J.L., Correas, I., Nieto, A. and Avila, J. (1988). Tau factor polymers are similar to paired helical filaments of Alzheimer's disease. FEBS Lett 236, 150-4.

[75]      Nieto, A., Correas, I., Montejo de Garcini, E. and Avila, J. (1988). A modified form of microtubule-associated tau protein is the main component of paired helical filaments. Biochem Biophys Res Commun 154, 660-7.

[76]      Serrano, L., Dominguez, J.E. and Avila, J. (1988). Identification of zinc-binding sites of proteins: zinc binds to the amino-terminal region of tubulin. Anal Biochem 172, 210-8.

[77]      Serrano, L., Wandosell, F., de la Torre, J. and Avila, J. (1988). Effect of specific proteolytic cleavages on tubulin polymer formation. Biochem J 252, 683-91.

[78]      Diaz-Nido, J. and Avila, J. (1989). Characterization of proteins immunologically related to brain microtubule-associated protein MAP-1B in non-neural cells. J Cell Sci 92 ( Pt 4), 607-20.

[79]      Diaz-Nido, J. and Avila, J. (1989). Quantitation of microtubule-associated protein MAP-1B in brain and other tissues. Int J Biochem 21, 723-30.

[80]      Hargreaves, A.J., Lamas, L., Santisteban, P. and Avila, J. (1989). Subcellular localization of iodinated thyroid tubulin. Biosci Rep 9, 375-82.

[81]      Hargreaves, A.J., Yusta, B., Avila, J., Hesketh, J.E., Aranda, A. and Pascual, A. (1989). Sodium butyrate induces major morphological changes in C6 glioma cells that are correlated with increased synthesis of a spectrin-like protein. Brain Res Dev Brain Res 45, 291-5.

[82]      Hernandez, M.A., Avila, J., Moya, F. and Alberto, C. (1989). Rearrangement of microtubule associated protein parallels the morphological transformation of neurons from dorsal root ganglion. Neuroscience 29, 471-7.

[83]      Maccioni, R.B., Vera, J.C., Dominguez, J. and Avila, J. (1989). A discrete repeated sequence defines a tubulin binding domain on microtubule-associated protein tau. Arch Biochem Biophys 275, 568-79.

[84]      Nieto, A., Montejo de Garcini, E. and Avila, J. (1989). Altered levels of microtubule proteins in brains of Alzheimer's disease patients. Acta Neuropathol (Berl) 78, 47-51.

[85]      Serrano, L., Diez, J.C., Wandosell, F., Avila, J. and Little, M. (1989). Calcium binding properties of the beta tubulin subunit from chicken erythrocytes. Biochem Int 19, 235-46.

[86]      Serrano, L., Hernandez, M.A., Diaz-Nido, J. and Avila, J. (1989). Association of casein kinase II with microtubules. Exp Cell Res 181, 263-72.

[87]      Stromberg, E., Serrano, L., Avila, J. and Wallin, M. (1989). Unusual properties of a cold-labile fraction of Atlantic cod (Gadus morhua) brain microtubules. Biochem Cell Biol 67, 791-800.

[88]      Avila, J. (1990). Microtubule dynamics. Faseb J 4, 3284-90.

[89]      Avila, J. (1990). Microtubule proteins. CRC Press. Boca Raton USA.

[90]      Casal, J., Gonzalez, C., Wandosell, F., Avila, J. and Ripoll, P. (1990). Abnormal meiotic spindles cause a cascade of defects during spermatogenesis in asp males of Drosophila. Development 108, 251-60.

[91]      Correas, I., Padilla, R. and Avila, J. (1990). The tubulin-binding sequence of brain microtubule-associated proteins, tau and MAP-2, is also involved in actin binding. Biochem J 269, 61-4.

[92]      Diaz-Nido, J. and Avila, J. (1990). Aluminum induces the in vitro aggregation of bovine brain cytoskeletal proteins. Neurosci Lett 110, 221-6.

[93]      Diaz-Nido, J., Serrano, L., Hernandez, M.A. and Avila, J. (1990). Phosphorylation of microtubule proteins in rat brain at different developmental stages: comparison with that found in neuronal cultures. J Neurochem 54, 211-22.

[94]      Diaz-Nido, J., Serrano, L., Lopez-Otin, C., Vandekerckhove, J. and Avila, J. (1990). Phosphorylation of a neuronal-specific beta-tubulin isotype. J Biol Chem 265, 13949-54.

[95]      Dominguez, J.E., Padilla, R., Avila, J. and Carrascosa, J.L. (1990). Removal of the carboxy terminus of beta-tubulin subunit produces lateral annealing of microtubules with different orientations. Int J Biochem 22, 1419-25.

[96]      Montejo de Garcini, E., Carrascosa, J.L., Nieto, A. and Avila, J. (1990). Collagenous structures present in brain contain epitopes shared by collagen and microtubule-associated protein tau. J Struct Biol 103, 34-9.

[97]      Nieto, A., Montejo de Garcini, E., Correas, I. and Avila, J. (1990). Characterization of tau protein present in microtubules and paired helical filaments of Alzheimer's disease patient's brain. Neuroscience 37, 163-70.

[98]      Padilla, R., Maccioni, R.B. and Avila, J. (1990). Calmodulin binds to a tubulin binding site of the microtubule-associated protein tau. Mol Cell Biochem 97, 35-41.

[99]      Rivas-Berrios, A., Hernandez, M.A., Dominguez, J., Avila, J. and Maccioni, R.B. (1990). Common antigenic determinants of the tubulin binding domains of the microtubule-associated proteins MAP-2 and tau. Biochim Biophys Acta 1040, 382-90.

[100]    Sanchez, A., Ossorio, C., Alvaro-Gracia, J.M., Padilla, R. and Avila, J. (1990). A subset of antibodies from the sera of patients with systemic lupus erythematosus react with vimentin and DNA. J Rheumatol 17, 205-9.

[101]    Armas-Portela, R., Kremer, L. and Avila, J. (1991). The centromere protein CENP-B behaves as a microtubule-associated protein. Acta Histochem Suppl 41, 37-43.

[102]    Avila, J. (1991). Does MAP1B bind to tubulin through the interaction of alpha-helices? Biochem J 274 ( Pt 2), 621-2.

[103]    Correas, I., Díaz-Nido, J. and Avila, J. (1991). The tubulin binding domain of tau proteins is phosphorylated by protein kinase C. J. Cell Biol. 115, 384 (Abstract).

[104]    Cross, D., Dominguez, J., Maccioni, R.B. and Avila, J. (1991). MAP-1 and MAP-2 binding sites at the C-terminus of beta-tubulin. Studies with synthetic tubulin peptides. Biochemistry 30, 4362-6.

[105]    Diaz-Nido, J., Armas-Portela, R. and Avila, J. (1991). Addition of protease inhibitors to culture medium of neuroblastoma cells induces both neurite outgrowth and phosphorylation of microtubule-associated protein MAP-1B. J Cell Sci 98 ( Pt 3), 409-14.

[106]    Diaz-Nido, J., Armas-Portela, R., Correas, I., Dominguez, J.E., Montejo, E. and Avila, J. (1991). Microtubule protein phosphorylation in neuroblastoma cells and neurite growth. J Cell Sci Suppl 15, 51-9.

[107]    Mansfield, S.G., Diaz-Nido, J., Gordon-Weeks, P.R. and Avila, J. (1991). The distribution and phosphorylation of the microtubule-associated protein MAP 1B in growth cones. J Neurocytol 20, 1007-22.

[108]    Munoz-Fernandez, M.A., Armas-Portela, R., Diaz-Nido, J., Alonso, J.L., Fresno, M. and Avila, J. (1991). Differential effects of tumor necrosis factor on the growth and differentiation of neuroblastoma and glioma cells. Exp Cell Res 194, 161-4.

[109]    Nieto, A., Correas, I., Lopez-Otin, C. and Avila, J. (1991). Tau-related protein present in paired helical filaments has a decreased tubulin binding capacity as compared with microtubule-associated protein tau. Biochim Biophys Acta 1096, 197-204.

[110]    Avila, J. (1992). Microtubule functions. Life Sci 50, 327-34.

[111]    Correas, I., Diaz-Nido, J. and Avila, J. (1992). Microtubule-associated protein tau is phosphorylated by protein kinase C on its tubulin binding domain. J Biol Chem 267, 15721-8.

[112]    Diaz-Nido, J., Armas-Portela, R. and Avila, J. (1992). Increase in cytoplasmic casein kinase II-type activity accompanies neurite outgrowth after DNA synthesis inhibition in NIA-103 neuroblastoma cells. J Neurochem 58, 1820-8.

[113]    Diaz-Nido, J. and Avila, J. (1992). Protein kinases associated with isolated mitotic spindles from mammalian cells: identification of a casein kinase II-like enzyme. Second Messengers Phosphoproteins 14, 39-53.

[114]    Gonzalez, P.J., Correas, I. and Avila, J. (1992). Solubilization and fractionation of paired helical filaments. Neuroscience 50, 491-9.

[115]    Ledesma, M.D., Correas, I., Avila, J. and Diaz-Nido, J. (1992). Implication of brain cdc2 and MAP2 kinases in the phosphorylation of tau protein in Alzheimer's disease. FEBS Lett 308, 218-24.

[116]    Montejo de Garcini, E., Corrochano, L., Wischik, C.M., Diaz Nido, J., Correas, I. and Avila, J. (1992). Differentiation of neuroblastoma cells correlates with an altered splicing pattern of tau RNA. FEBS Lett 299, 10-4.

[117]    Ramos-Ruiz, R., Avila, J., Lopez-Bote, J.P., Bernabeu, C. and Larraga, V. (1992). Decreased tubulin synthesis in synoviocytes from adjuvant-induced arthritic rats. Biochim Biophys Acta 1138, 184-90.

[118]    de Ancos, J.G. and Avila, J. (1993). Differential distribution in white and grey matter of tau phosphoisoforms containing four tubulin-binding motifs. Biochem J 296 ( Pt 2), 351-4.

[119]    Diaz-Nido, J., Montoro, R.J., Lopez-Barneo, J. and Avila, J. (1993). High external potassium induces an increase in the phosphorylation of the cytoskeletal protein MAP2 in rat hippocampal slices. Eur J Neurosci 5, 818-24.

[120]    Diez-Guerra, F.J. and Avila, J. (1993). Rapid dephosphorylation of microtubule-associated protein 2 in the rat brain hippocampus after pentylenetetrazole-induced seizures. Eur J Biochem 215, 181-7.

[121]    Diez-Guerra, F.J. and Avila, J. (1993). MAP2 phosphorylation parallels dendrite arborization in hippocampal neurones in culture. Neuroreport 4, 419-22.

[122]    Fontalba, A., Paciucci, R., Avila, J. and Zabala, J.C. (1993). Incorporation of tubulin subunits into dimers requires GTP hydrolysis. J Cell Sci 106 ( Pt 2), 627-32.

[123]    Garcia de Ancos, J., Correas, I. and Avila, J. (1993). Differences in microtubule binding and self-association abilities of bovine brain tau isoforms. J Biol Chem 268, 7976-82.

[124]    Montoro, R.J., Diaz-Nido, J., Avila, J. and Lopez-Barneo, J. (1993). N-methyl-D-aspartate stimulates the dephosphorylation of the microtubule-associated protein 2 and potentiates excitatory synaptic pathways in the rat hippocampus. Neuroscience 54, 859-71.

[125]    Padilla, R., Lopez Otin, C., Serrano, L. and Avila, J. (1993). Role of the carboxy terminal region of beta tubulin on microtubule dynamics through its interaction with the GTP phosphate binding region. FEBS Lett 325, 173-6.

[126]    Ulloa, L., Avila, J. and Diaz-Nido, J. (1993). Heterogeneity in the phosphorylation of microtubule-associated protein MAP1B during rat brain development. J Neurochem 61, 961-72.

[127]    Ulloa, L., Diaz-Nido, J. and Avila, J. (1993). Depletion of casein kinase II by antisense oligonucleotide prevents neuritogenesis in neuroblastoma cells. Embo J 12, 1633-40.

[128]    Ulloa, L., Dombradi, V., Diaz-Nido, J., Szucs, K., Gergely, P., Friedrich, P. and Avila, J. (1993). Dephosphorylation of distinct sites on microtubule-associated protein MAP1B by protein phosphatases 1, 2A and 2B. FEBS Lett 330, 85-9.

[129]    Avila, J., Dominguez, J. and Diaz-Nido, J. (1994). Regulation of microtubule dynamics by microtubule-associated protein expression and phosphorylation during neuronal development. Int J Dev Biol 38, 13-25.

[130]    Cross, D., Farias, G., Dominguez, J., Avila, J. and Maccioni, R.B. (1994). Carboxyl terminal sequences of beta-tubulin involved in the interaction of HMW-MAPs. Studies using site-specific antibodies. Mol Cell Biochem 132, 81-90.

[131]    Dominguez, J.E., Buendia, B., Lopez-Otin, C., Antony, C., Karsenti, E. and Avila, J. (1994). A protein related to brain microtubule-associated protein MAP1B is a component of the mammalian centrosome. J Cell Sci 107 ( Pt 2), 601-11.

[132]    Garcia-Rocha, M., Avila, J. and Armas-Portela, R. (1994). Tissue-type plasminogen activator (tPA) is the main plasminogen activator associated with isolated rat nerve growth cones. Neurosci Lett 180, 123-6.

[133]    Gonzalez-Nicolas, J., Medina, M., Fermin, Y., Moreno, F. and Avila, J. (1994). Identification of protein kinases that modify specific epitopes. Anal Biochem 223, 159-61.

[134]    Ledesma, M.D., Bonay, P., Colaco, C. and Avila, J. (1994). Analysis of microtubule-associated protein tau glycation in paired helical filaments. J Biol Chem 269, 21614-9.

[135]    Montejo de Garcini, E., de la Luna, S., Dominguez, J.E. and Avila, J. (1994). Overexpression of tau protein in COS-1 cells results in the stabilization of centrosome-independent microtubules and extension of cytoplasmic processes. Mol Cell Biochem 130, 187-96.

[136]    Pazzagli, C. and Avila, J. (1994). Purification of brain microtubule-associated protein MAP1A. Neurochem Res 19, 1195-8.

[137]    Sanchez, C., Padilla, R., Paciucci, R., Zabala, J.C. and Avila, J. (1994). Binding of heat-shock protein 70 (hsp70) to tubulin. Arch Biochem Biophys 310, 428-32.

[138]    Szucs, K., Ledesma, M.D., Dombradi, V., Gergely, P., Avila, J. and Friedrich, P. (1994). Dephosphorylation of tau protein from Alzheimer's disease patients. Neurosci Lett 165, 175-8.

[139]    Ulloa, L., Diaz-Nido, J. and Avila, J. (1994). Depletion of catalytic and regulatory subunits of protein kinase CK2 by antisense oligonucleotide treatment of neuroblastoma cells. Cell Mol Neurobiol 14, 407-14.

[140]    Ulloa, L., Diez-Guerra, F.J., Avila, J. and Diaz-Nido, J. (1994). Localization of differentially phosphorylated isoforms of microtubule-associated protein 1B in cultured rat hippocampal neurons. Neuroscience 61, 211-23.

[141]    Ulloa, L., Ibarrola, N., Avila, J. and Diez-Guerra, F.J. (1994). Microtubule-associated protein 1B (MAP1B) is present in glial cells phosphorylated different than in neurones. Glia 10, 266-75.

[142]    Ulloa, L., Montejo de Garcini, E., Gomez-Ramos, P., Moran, M.A. and Avila, J. (1994). Microtubule-associated protein MAP1B showing a fetal phosphorylation pattern is present in sites of neurofibrillary degeneration in brains of Alzheimer's disease patients. Brain Res Mol Brain Res 26, 113-22.

[143]    Avila, J. (1995). Tau phosphorylation and neurite extension. Different phosphorylation sites different kinases, different consequences. Neurobiol. Aging 16, 475-476.

[144]    Diez-Guerra, F.J. and Avila, J. (1995). An increase in phosphorylation of microtubule-associated protein 2 accompanies dendrite extension during the differentiation of cultured hippocampal neurones. Eur J Biochem 227, 68-77.

[145]    Fontalba, A., Avila, J. and Zabala, J.C. (1995). Beta-tubulin folding is modulated by the isotype-specific carboxy-terminal domain. J Mol Biol 246, 628-36.

[146]    Garcia Rocha, M. and Avila, J. (1995). Characterization of microtubule-associated protein phosphoisoforms present in isolated growth cones. Brain Res Dev Brain Res 89, 47-55.

[147]    Ledesma, M.D., Avila, J. and Correas, I. (1995). Isolation of a phosphorylated soluble tau fraction from Alzheimer's disease brain. Neurobiol Aging 16, 515-22.

[148]    Ledesma, M.D., Bonay, P. and Avila, J. (1995). Tau protein from Alzheimer's disease patients is glycated at its tubulin-binding domain. J Neurochem 65, 1658-64.

[149]    Medina, M., Montejo de Garcini, E. and Avila, J. (1995). The role of tau phosphorylation in transfected COS-1 cells. Mol Cell Biochem 148, 79-88.

[150]    Moreno, F.J., Medina, M., Perez, M., Montejo de Garcini, E. and Avila, J. (1995). Glycogen synthase kinase 3 phosphorylates recombinant human tau protein at serine-262 in the presence of heparin (or tubulin). FEBS Lett 372, 65-8.

[151]    Sanchez, C., Diaz-Nido, J. and Avila, J. (1995). Variations in in vivo phosphorylation at the proline-rich domain of the microtubule-associated protein 2 (MAP2) during rat brain development. Biochem J 306 ( Pt 2), 481-7.

[152]    Vial, C., Armas-Portela, R., Avila, J., Gonzalez, M. and Maccioni, R.B. (1995). A 205 kDa protein from non-neuronal cells in culture contains tubulin binding epitopes. Mol Cell Biochem 144, 109-116.

[153]    Avila, J. (1996). Intercellular signals and the cytoskeleton. Seminars in Develop. Biology 7, 681.

[154]    Avila, J., Pérez, M., Montejo, E. and Medina, M. (1996). Posttranslational modifications of tau and the formation of paired helical filaments. Neurobiol. Aging 17, 5188 (Abstract).

[155]    Díaz-Nido, J., Ulloa, L., Sánchez, C. and Avila, J. (1996). The role of the cytoskeleton in the morphological changes occurring during neuronal differentiation. Seminar in Develop. Biology 7, 733-740.

[156]    Garcia-Rocha, M., Bonay, P. and Avila, J. (1996). The antitumoral compound Kahalalide F acts on cell lysosomes. Cancer Lett 99, 43-50.

[157]    Garcia-Rocha, M., Garcia-Gravalos, M.D. and Avila, J. (1996). Characterisation of antimitotic products from marine organisms that disorganise the microtubule network: ecteinascidin 743, isohomohalichondrin-B and LL-15. Br J Cancer 73, 875-83.

[158]    Ledesma, M.D., Medina, M. and Avila, J. (1996). The in vitro formation of recombinant tau polymers: effect of phosphorylation and glycation. Mol Chem Neuropathol 27, 249-58.

[159]    Ledesma, M.D., Moreno, F.J., Pérez, M. and Avila, J. (1996). Binding of apolipoprotein E3 to tau protein: effects on tau glycation, tau phosphorylation and tau-microtubule bindings in vitro. Alzheimer's Res. 2, 120-124.

[160]    Llosa, M., Aloria, K., Campo, R., Padilla, R., Avila, J., Sanchez-Pulido, L. and Zabala, J.C. (1996). The beta-tubulin monomer release factor (p14) has homology with a region of the DnaJ protein. FEBS Lett 397, 283-9.

[161]    Medina, M., Garcia-Rocha, M., Padilla, R., Perez, M., Montejo de Garcini, E. and Avila, J. (1996). Protein kinases involved in the phosphorylation of human tau protein in transfected COS-1 cells. Biochim Biophys Acta 1316, 43-50.

[162]    Moreno, F.J., Munoz-Montano, J.R. and Avila, J. (1996). Glycogen synthase kinase 3 phosphorylation of different residues in the presence of different factors: analysis on tau protein. Mol Cell Biochem 165, 47-54.

[163]    Pedrotti, B., Ulloa, L., Avila, J. and Islam, K. (1996). Characterization of microtubule-associated protein MAP1B: phosphorylation state, light chains, and binding to microtubules. Biochemistry 35, 3016-23.

[164]    Perez, M., Valpuesta, J.M., Medina, M., Montejo de Garcini, E. and Avila, J. (1996). Polymerization of tau into filaments in the presence of heparin: the minimal sequence required for tau-tau interaction. J Neurochem 67, 1183-90.

[165]    Sanchez, C., Tompa, P., Szucs, K., Friedrich, P. and Avila, J. (1996). Phosphorylation and dephosphorylation in the proline-rich C-terminal domain of microtubule-associated protein 2. Eur J Biochem 241, 765-71.

[166]    Ulloa, L. and Avila, J. (1996). Involvement of gamma and beta actin isoforms in mouse neuroblastoma differentiation. Eur J Neurosci 8, 1441-51.

[167]    Zabala, J.C., Fontalba, A. and Avila, J. (1996). Tubulin folding is altered by mutations in a putative GTP binding motif. J Cell Sci 109 ( Pt 6), 1471-8.

[168]    Arrasate, M., Perez, M., Valpuesta, J.M. and Avila, J. (1997). Role of glycosaminoglycans in determining the helicity of paired helical filaments. Am J Pathol 151, 1115-22.

[169]    Avila, J. (1997). The use of microtubule poisons on tumor cells. The Cancer J. 10, 315-318.

[170]    Avila, J. and Colaço, A.L.S. (1997). The role of sulfated glycosaminoglycans in Alzheimer's disease: a hypothesis. Alzheimer's Research 3, 77-81.

[171]    Garcia-Rocha, M., Avila, J. and Lozano, J. (1997). The zeta isozyme of protein kinase C binds to tubulin through the pseudosubstrate domain. Exp Cell Res 230, 1-8.

[172]    Munoz-Montano, J.R., Moreno, F.J., Avila, J. and Diaz-Nido, J. (1997). Lithium inhibits Alzheimer's disease-like tau protein phosphorylation in neurons. FEBS Lett 411, 183-8.

[173]    Perez, M., Aloria, K., Zabala, J.C. and Avila, J. (1997). A putative beta-tubulin phosphate-binding motif is involved in lateral microtubule protofilament interactions. Eur J Biochem 248, 840-7.

[174]    Pigino, G., Paglini, G., Ulloa, L., Avila, J. and Caceres, A. (1997). Analysis of the expression, distribution and function of cyclin dependent kinase 5 (cdk5) in developing cerebellar macroneurons. J Cell Sci 110 ( Pt 2), 257-70.

[175]    Ramon-Cueto, A. and Avila, J. (1997). Differential expression of microtubule-associated protein 1B phosphorylated isoforms in the adult rat nervous system. Neuroscience 77, 485-501.

[176]    Sanchez, C., Ulloa, L., Montoro, R.J., Lopez-Barneo, J. and Avila, J. (1997). NMDA-glutamate receptors regulate phosphorylation of dendritic cytoskeletal proteins in the hippocampus. Brain Res 765, 141-8.

[177]    Fanarraga, M.L., Aloria, K., Avila, J. and Zabala, J.C. (1998). Characterization of tubulin isotype-specific antibodies by electrophoretic mobility shift assay. Biotechniques 25, 940-2.

[178]    Franco, P. et al. (1998). Protein kinase C-dependent in vivo phosphorylation of prourokinase leads to the formation of a receptor competitive antagonist. J Biol Chem 273, 27734-40.

[179]    Garcia-Perez, J., Avila, J. and Diaz-Nido, J. (1998). Implication of cyclin-dependent kinases and glycogen synthase kinase 3 in the phosphorylation of microtubule-associated protein 1B in developing neuronal cells. J Neurosci Res 52, 445-52.

[180]    Heredia, M., Gascuel, J., Ramon-Cueto, A., Santacana, M., Avila, J., Masson, C. and Valverde, F. (1998). Two novel monoclonal antibodies (1.9.E and 4.11.C) against olfactory bulb ensheathing glia. Glia 24, 352-64.

[181]    Moreno, F.J. and Avila, J. (1998). Phosphorylation of stathmin modulates its function as a microtubule depolymerizing factor. Mol Cell Biochem 183, 201-9.

[182]    Perez, M. et al. (1998). Ferritin is associated with the aberrant tau filaments present in progressive supranuclear palsy. Am J Pathol 152, 1531-9.

[183]    Perez, M., Wandosell, F., Colaco, C. and Avila, J. (1998). Sulphated glycosaminoglycans prevent the neurotoxicity of a human prion protein fragment. Biochem J 335 ( Pt 2), 369-74.

[184]    Ramon-Cueto, A. and Avila, J. (1998). Olfactory ensheathing glia: properties and function. Brain Res Bull 46, 175-87.

[185]    Ramon-Cueto, A., Plant, G.W., Avila, J. and Bunge, M.B. (1998). Long-distance axonal regeneration in the transected adult rat spinal cord is promoted by olfactory ensheathing glia transplants. J Neurosci 18, 3803-15.

[186]    Sanchez Martin, C., Diaz-Nido, J. and Avila, J. (1998). Regulation of a site-specific phosphorylation of the microtubule-associated protein 2 during the development of cultured neurons. Neuroscience 87, 861-70.

[187]    Vecino, E., Ulloa, L. and Avila, J. (1998). The phosphorylated isoform of microtubule associated protein 1B (MAP1B) is expressed in the visual system of the tench (Tinca tinca, L) during optic nerve regeneration. Neurosci Lett 245, 93-6.

[188]    Alvarez, G., Munoz-Montano, J.R., Satrustegui, J., Avila, J., Bogonez, E. and Diaz-Nido, J. (1999). Lithium protects cultured neurons against beta-amyloid-induced neurodegeneration. FEBS Lett 453, 260-4.

[189]    Armas-Portela, R., Parrales, M.A., Albar, J.P., Martinez, A.C. and Avila, J. (1999). Distribution and characteristics of betaII tubulin-enriched microtubules in interphase cells. Exp Cell Res 248, 372-80.

[190]    Arrasate, M., Perez, M., Armas-Portela, R. and Avila, J. (1999). Polymerization of tau peptides into fibrillar structures. The effect of FTDP-17 mutations. FEBS Lett 446, 199-202.

[191]    Avila, J. (1999). Eladio Vinuela (1937-1999), the molecular biology pioneer in Spain. Int Microbiol 2, 119-20.

[192]    Avila, J. and Mayor, F., Jr. (1999). Eladio Vinuela (1937-99). Nature 400, 822.

[193]    Fanarraga, M.L., Avila, J. and Zabala, J.C. (1999). Expression of unphosphorylated class III beta-tubulin isotype in neuroepithelial cells demonstrates neuroblast commitment and differentiation. Eur J Neurosci 11, 517-27.

[194]    Fanarraga, M.L., Parraga, M., Aloria, K., del Mazo, J., Avila, J. and Zabala, J.C. (1999). Regulated expression of p14 (cofactor A) during spermatogenesis. Cell Motil Cytoskeleton 43, 243-54.

[195]    Garcia-Perez, J., Avila, J. and Diaz-Nido, J. (1999). Lithium induces morphological differentiation of mouse neuroblastoma cells. J Neurosci Res 57, 261-70.

[196]    Hoenicka, J. et al. (1999). The tau gene A0 allele and progressive supranuclear palsy. Neurology 53, 1219-25.

[197]    Lucas, J.J., Hernandez, F. and Avila, J. (1999). Nuclear localization of beta-catenin in adult mouse thalamus correlates with low levels of GSK-3beta. Neuroreport 10, 2699-703.

[198]    Moreno, F.J., Bagnat, M., Lim, F. and Avila, J. (1999). OP18/stathmin binds near the C-terminus of tubulin and facilitates GTP binding. Eur J Biochem 262, 557-62.

[199]    Moreno, F.J., Diaz-Nido, J., Jimenez, J.S. and Avila, J. (1999). Distribution of CK2, its substrate MAP1B and phosphatases in neuronal cells. Mol Cell Biochem 191, 201-5.

[200]    Munoz-Montano, J.R., Moreno, F.J., Avila, J. and Diaz-Nido, J. (1999). Downregulation of glycogen synthase kinase-3beta (GSK-3beta) protein expression during neuroblastoma IMR-32 cell differentiation. J Neurosci Res 55, 278-85.

[201]    Perez, M. and Avila, J. (1999). The expression of casein kinase 2alpha' and phosphatase 2A activity. Biochim Biophys Acta 1449, 150-6.

[202]    Ramon-Cueto, A. and Avila, J. (1999). Two modes of microtubule-associated protein 1B phosphorylation are differentially regulated during peripheral nerve regeneration. Brain Res 815, 213-26.

[203]    Sayas, C.L., Moreno-Flores, M.T., Avila, J. and Wandosell, F. (1999). The neurite retraction induced by lysophosphatidic acid increases Alzheimer's disease-like Tau phosphorylation. J Biol Chem 274, 37046-52.

[204]    Zambrano, R., Briones, E., Avila, J. and Ballesta, J.P. (1999). Phosphorylation of P'(1) serine inhibits peptide bond sensitivity to Staphylococcus aureus V8 protease. Arch Biochem Biophys 368, 207-9.

[205]    Arrasate, M., Perez, M. and Avila, J. (2000). Tau dephosphorylation at tau-1 site correlates with its association to cell membrane. Neurochem Res 25, 43-50.

[206]    Avila, J. (2000). Tau aggregation into fibrillar polymers: taupathies. FEBS Lett 476, 89-92.

[207]    Bullido, M.J., Aldudo, J., Frank, A., Coria, F., Avila, J. and Valdivieso, F. (2000). A polymorphism in the tau gene associated with risk for Alzheimer's disease. Neurosci Lett 278, 49-52.

[208]    Cuadros, R., Montejo de Garcini, E., Wandosell, F., Faircloth, G., Fernandez-Sousa, J.M. and Avila, J. (2000). The marine compound spisulosine, an inhibitor of cell proliferation, promotes the disassembly of actin stress fibers. Cancer Lett 152, 23-9.

[209]    Gong, C.X., Wegiel, J., Lidsky, T., Zuck, L., Avila, J., Wisniewski, H.M., Grundke-Iqbal, I. and Iqbal, K. (2000). Regulation of phosphorylation of neuronal microtubule-associated proteins MAP1b and MAP2 by protein phosphatase-2A and -2B in rat brain. Brain Res 853, 299-309.

[210]    Gonzalez-Billault, C. and Avila, J. (2000). Molecular genetic approaches to microtubule-associated protein function. Histol Histopathol 15, 1177-83.

[211]    Gonzalez-Billault, C. et al. (2000). Perinatal lethality of microtubule-associated protein 1B-deficient mice expressing alternative isoforms of the protein at low levels. Mol Cell Neurosci 16, 408-21.

[212]    Jimenez, C. et al. (2000). Role of the PI3K regulatory subunit in the control of actin organization and cell migration. J Cell Biol 151, 249-62.

[213]    Perez, M., Cuadros, R., Smith, M.A., Perry, G. and Avila, J. (2000). Phosphorylated, but not native, tau protein assembles following reaction with the lipid peroxidation product, 4-hydroxy-2-nonenal. FEBS Lett 486, 270-4.

[214]    Perez, M., Lim, F., Arrasate, M. and Avila, J. (2000). The FTDP-17-linked mutation R406W abolishes the interaction of phosphorylated tau with microtubules. J Neurochem 74, 2583-9.

[215]    Ramon-Cueto, A., Cordero, M.I., Santos-Benito, F.F. and Avila, J. (2000). Functional recovery of paraplegic rats and motor axon regeneration in their spinal cords by olfactory ensheathing glia. Neuron 25, 425-35.

[216]    Sanchez, C., Diaz-Nido, J. and Avila, J. (2000). Phosphorylation of microtubule-associated protein 2 (MAP2) and its relevance for the regulation of the neuronal cytoskeleton function. Prog Neurobiol 61, 133-68.

[217]    Sanchez, C., Perez, M. and Avila, J. (2000). GSK3beta-mediated phosphorylation of the microtubule-associated protein 2C (MAP2C) prevents microtubule bundling. Eur J Cell Biol 79, 252-60.

[218]    Sanchez Martin, C., Ledesma, D., Dotti, C.G. and Avila, J. (2000). Microtubule-associated protein-2 located in growth regions of rat hippocampal neurons is highly phosphorylated at its proline-rich region. Neuroscience 101, 885-93.

[219]    Takeda, A., Smith, M.A., Avila, J., Nunomura, A., Siedlak, S.L., Zhu, X., Perry, G. and Sayre, L.M. (2000). In Alzheimer's disease, heme oxygenase is coincident with Alz50, an epitope of tau induced by 4-hydroxy-2-nonenal modification. J Neurochem 75, 1234-41.

[220]    Bonay, P. and Avila, J. (2001). Apolipoprotein E4 stimulates sulfation of glycosaminoglycans in neural cells. Biochim Biophys Acta 1535, 217-20.

[221]    Gonzalez-Billault, C., Avila, J. and Caceres, A. (2001). Evidence for the role of MAP1B in axon formation. Mol Biol Cell 12, 2087-98.

[222]    Lim, F., Hernandez, F., Lucas, J.J., Gomez-Ramos, P., Moran, M.A. and Avila, J. (2001). FTDP-17 mutations in tau transgenic mice provoke lysosomal abnormalities and Tau filaments in forebrain. Mol Cell Neurosci 18, 702-14.

[223]    Lopez-Fanarraga, M., Avila, J., Guasch, A., Coll, M. and Zabala, J.C. (2001). Review: postchaperonin tubulin folding cofactors and their role in microtubule dynamics. J Struct Biol 135, 219-29.

[224]    Lorio, G., Avila, J. and Diaz-Nido, J. (2001). Modifications of tau protein during neuronal cell death. J Alzheimers Dis 3, 563-575.

[225]    Lucas, J.J., Hernandez, F., Gomez-Ramos, P., Moran, M.A., Hen, R. and Avila, J. (2001). Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice. Embo J 20, 27-39.

[226]    Martin-Aparicio, E., Yamamoto, A., Hernandez, F., Hen, R., Avila, J. and Lucas, J.J. (2001). Proteasomal-dependent aggregate reversal and absence of cell death in a conditional mouse model of Huntington's disease. J Neurosci 21, 8772-81.

[227]    Moreno-Herrero, F., Valpuesta, J.M., Perez, M., Colchero, J., Baro, A.M., Avila, J. and Montejo De Garcini, E. (2001). Characterization by atomic force microscopy and cryoelectron microscopy of tau polymers assembled in Alzheimer's disease. J Alzheimers Dis 3, 443-451.

[228]    Perez, M., Arrasate, M., Montejo De Garcini, E., Munoz, V. and Avila, J. (2001). In vitro assembly of tau protein: mapping the regions involved in filament formation. Biochemistry 40, 5983-91.

[229]    Perry, G., Avila, J., Espey, M.G., Wink, D.A., Atwood, C.S. and Smith, M.A. (2001). Biochemistry of neurodegeneration. Science 291, 595-7.

[230]    Sanchez, C., Arellano, J.I., Rodriguez-Sanchez, P., Avila, J., DeFelipe, J. and Diez-Guerra, F.J. (2001). Microtubule-associated protein 2 phosphorylation is decreased in the human epileptic temporal lobe cortex. Neuroscience 107, 25-33.

[231]    Sanchez, S., Sayas, C.L., Lim, F., Diaz-Nido, J., Avila, J. and Wandosell, F. (2001). The inhibition of phosphatidylinositol-3-kinase induces neurite retraction and activates GSK3. J Neurochem 78, 468-81.

[232]    Vecino, E. and Avila, J. (2001). Distribution of the phosphorylated form of microtubule associated protein 1B in the fish visual system during optic nerve regeneration. Brain Res Bull 56, 131-7.

[233]    Agudo, M., Trejo, J.L., Lim, F., Avila, J., Torres-Aleman, I., Diaz-Nido, J. and Wandosell, F. (2002). Highly efficient and specific gene transfer to Purkinje cells in vivo using a herpes simplex virus I amplicon. Hum Gene Ther 13, 665-74.

[234]    Alvarez, G., Munoz-Montano, J.R., Satrustegui, J., Avila, J., Bogonez, E. and Diaz-Nido, J. (2002). Regulation of tau phosphorylation and protection against beta-amyloid-induced neurodegeneration by lithium. Possible implications for Alzheimer's disease. Bipolar Disord 4, 153-65.

[235]    Avila, J., Lim, F., Moreno, F., Belmonte, C. and Cuello, A.C. (2002). Tau function and dysfunction in neurons: its role in neurodegenerative disorders. Mol Neurobiol 25, 213-31.

[236]    Diaz-Nido, J., Wandosell, F. and Avila, J. (2002). Glycosaminoglycans and beta-amyloid, prion and tau peptides in neurodegenerative diseases. Peptides 23, 1323-32.

[237]    Gonzalez-Billault, C., Engelke, M., Jimenez-Mateos, E.M., Wandosell, F., Caceres, A. and Avila, J. (2002). Participation of structural microtubule-associated proteins (MAPs) in the development of neuronal polarity. J Neurosci Res 67, 713-9.

[238]    Gonzalez-Billault, C., Owen, R., Gordon-Weeks, P.R. and Avila, J. (2002). Microtubule-associated protein 1B is involved in the initial stages of axonogenesis in peripheral nervous system cultured neurons. Brain Res 943, 56-67.

[239]    Guasch, A., Aloria, K., Perez, R., Avila, J., Zabala, J.C. and Coll, M. (2002). Three-dimensional structure of human tubulin chaperone cofactor A. J Mol Biol 318, 1139-49.

[240]    Hartzler, A.W., Zhu, X., Siedlak, S.L., Castellani, R.J., Avila, J., Perry, G. and Smith, M.A. (2002). The p38 pathway is activated in Pick disease and progressive supranuclear palsy: a mechanistic link between mitogenic pathways, oxidative stress, and tau. Neurobiol Aging 23, 855-9.

[241]    Hernandez, F., Borrell, J., Guaza, C., Avila, J. and Lucas, J.J. (2002). Spatial learning deficit in transgenic mice that conditionally over-express GSK-3beta in the brain but do not form tau filaments. J Neurochem 83, 1529-33.

[242]    Hernandez, F., Lim, F., Lucas, J.J., Perez-Martin, C., Moreno, F. and Avila, J. (2002). Transgenic mouse models with tau pathology to test therapeutic agents for Alzheimer's disease. Mini Rev Med Chem 2, 51-8.

[243]    Hernandez, F., Perez, M., Lucas, J.J. and Avila, J. (2002). Sulfo-glycosaminoglycan content affects PHF-tau solubility and allows the identification of different types of PHFs. Brain Res 935, 65-72.

[244]    Hoenicka, J., Arrasate, M., de Yebenes, J.G. and Avila, J. (2002). A two-hybrid screening of human Tau protein: interactions with Alu-derived domain. Neuroreport 13, 343-9.

[245]    Martin, C.P., Vazquez, J., Avila, J. and Moreno, F.J. (2002). P24, a glycogen synthase kinase 3 (GSK 3) inhibitor. Biochim Biophys Acta 1586, 113-22.

[246]    Martin-Aparicio, E., Avila, J. and Lucas, J.J. (2002). Nuclear localization of N-terminal mutant huntingtin is cell cycle dependent. Eur J Neurosci 16, 355-9.

[247]    Moreno-Flores, M.T., Diaz-Nido, J., Wandosell, F. and Avila, J. (2002). Olfactory Ensheathing Glia: Drivers of Axonal Regeneration in the Central Nervous System? J Biomed Biotechnol 2, 37-43.

[248]    Moreno-Flores, M.T., Martin-Aparicio, E., Avila, J., Diaz-Nido, J. and Wandosell, F. (2002). Ephrin-B1 promotes dendrite outgrowth on cerebellar granule neurons. Mol Cell Neurosci 20, 429-46.

[249]    Perez, M., Hernandez, F., Gomez-Ramos, A., Smith, M., Perry, G. and Avila, J. (2002). Formation of aberrant phosphotau fibrillar polymers in neural cultured cells. Eur J Biochem 269, 1484-9.

[250]    Perry, G. et al. (2002). Reactive oxygen: its sources and significance in Alzheimer disease. J Neural Transm Suppl, 69-75.

[251]    Perry, G. et al. (2002). Is oxidative damage the fundamental pathogenic mechanism of Alzheimer's and other neurodegenerative diseases? Free Radic Biol Med 33, 1475-9.

[252]    Sadqi, M., Hernandez, F., Pan, U., Perez, M., Schaeberle, M.D., Avila, J. and Munoz, V. (2002). Alpha-helix structure in Alzheimer's disease aggregates of tau-protein. Biochemistry 41, 7150-5.

[253]    Sanchez, M.P., Gonzalo, I., Avila, J. and De Yebenes, J.G. (2002). Progressive supranuclear palsy and tau hyperphosphorylation in a patient with a C212Y parkin mutation. J Alzheimers Dis 4, 399-404.

[254]    Sayas, C.L., Avila, J. and Wandosell, F. (2002). Glycogen synthase kinase-3 is activated in neuronal cells by Galpha12 and Galpha13 by Rho-independent and Rho-dependent mechanisms. J Neurosci 22, 6863-75.

[255]    Sayas, C.L., Avila, J. and Wandosell, F. (2002). Regulation of neuronal cytoskeleton by lysophosphatidic acid: role of GSK-3. Biochim Biophys Acta 1582, 144-53.

[256]    Wataya, T. et al. (2002). High molecular weight neurofilament proteins are physiological substrates of adduction by the lipid peroxidation product hydroxynonenal. J Biol Chem 277, 4644-8.

[257]    Bhat, R. et al. (2003). Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418. J Biol Chem 278, 45937-45.

[258]    Cash, A.D. et al. (2003). Microtubule reduction in Alzheimer's disease and aging is independent of tau filament formation. Am J Pathol 162, 1623-7.

[259]    Diaz-Hernandez, M. et al. (2003). Neuronal induction of the immunoproteasome in Huntington's disease. J Neurosci 23, 11653-61.

[260]    Gomez-Ramos, A., Diaz-Nido, J., Smith, M.A., Perry, G. and Avila, J. (2003). Effect of the lipid peroxidation product acrolein on tau phosphorylation in neural cells. J Neurosci Res 71, 863-70.

[261]    Hernandez, F., Lucas, J.J., Cuadros, R. and Avila, J. (2003). GSK-3 dependent phosphoepitopes recognized by PHF-1 and AT-8 antibodies are present in different tau isoforms. Neurobiol Aging 24, 1087-94.

[262]    Moreno-Flores, M.T., Lim, F., Martin-Bermejo, M.J., Diaz-Nido, J., Avila, J. and Wandosell, F. (2003). Immortalized olfactory ensheathing glia promote axonal regeneration of rat retinal ganglion neurons. J Neurochem 85, 861-71.

[263]    Moreno-Flores, M.T., Lim, F., Martin-Bermejo, M.J., Diaz-Nido, J., Avila, J. and Wandosell, F. (2003). High level of amyloid precursor protein expression in neurite-promoting olfactory ensheathing glia (OEG) and OEG-derived cell lines. J Neurosci Res 71, 871-81.

[264]    Moreno-Flores, M.T., Martin-Aparicio, E., Martin-Bermejo, M.J., Agudo, M., McMahon, S., Avila, J., Diaz-Nido, J. and Wandosell, F. (2003). Semaphorin 3C preserves survival and induces neuritogenesis of cerebellar granule neurons in culture. J Neurochem 87, 879-90.

[265]    Perez, M., Hernandez, F., Lim, F., Diaz-Nido, J. and Avila, J. (2003). Chronic lithium treatment decreases mutant tau protein aggregation in a transgenic mouse model. J Alzheimers Dis 5, 301-8.

[266]    Perez, M., Rojo, A.I., Wandosell, F., Diaz-Nido, J. and Avila, J. (2003). Prion peptide induces neuronal cell death through a pathway involving glycogen synthase kinase 3. Biochem J 372, 129-36.

[267]    Perez, M., Sadqi, M., Munoz, V. and Avila, J. (2003). Inhibition by Aplidine of the aggregation of the prion peptide PrP 106-126 into beta-sheet fibrils. Biochim Biophys Acta 1639, 133-9.

[268]    Avila, J. (2004). The influence of aging in one tauopathy: Alzheimer 's disease. Arch Immunol Ther Exp (Warsz) 52, 410-3.

[269]    Avila, J. and Diaz-Nido, J. (2004). Tangling with hypothermia. Nat Med 10, 460-1.

[270]    Avila, J., Lucas, J.J., Perez, M. and Hernandez, F. (2004). Role of tau protein in both physiological and pathological conditions. Physiol Rev 84, 361-84.

[271]    Avila, J., Perez, M., Lim, F., Gomez-Ramos, A., Hernandez, F. and Lucas, J.J. (2004). Tau in neurodegenerative diseases: tau phosphorylation and assembly. Neurotox Res 6, 477-82.

[272]    Avila, J. et al. (2004). Assembly in vitro of tau protein and its implications in Alzheimer's disease. Curr Alzheimer Res 1, 97-101.

[273]    Bhat, R.V., Budd Haeberlein, S.L. and Avila, J. (2004). Glycogen synthase kinase 3: a drug target for CNS therapies. J Neurochem 89, 1313-7.

[274]    Cardona-Gomez, P., Perez, M., Avila, J., Garcia-Segura, L.M. and Wandosell, F. (2004). Estradiol inhibits GSK3 and regulates interaction of estrogen receptors, GSK3, and beta-catenin in the hippocampus. Mol Cell Neurosci 25, 363-73.

[275]    Del Rio, J.A. et al. (2004). MAP1B is required for Netrin 1 signaling in neuronal migration and axonal guidance. Curr Biol 14, 840-50.

[276]    Diaz-Hernandez, M., Martin-Aparicio, E., Avila, J., Hernandez, F. and Lucas, J.J. (2004). Enhanced induction of the immunoproteasome by interferon gamma in neurons expressing mutant Huntingtin. Neurotox Res 6, 463-8.

[277]    Diaz-Hernandez, M. et al. (2004). Biochemical, ultrastructural, and reversibility studies on huntingtin filaments isolated from mouse and human brain. J Neurosci 24, 9361-71.

[278]    Echeverria, V. et al. (2004). Altered mitogen-activated protein kinase signaling, tau hyperphosphorylation and mild spatial learning dysfunction in transgenic rats expressing the beta-amyloid peptide intracellularly in hippocampal and cortical neurons. Neuroscience 129, 583-92.

[279]    Farias, G.G., Godoy, J.A., Hernandez, F., Avila, J., Fisher, A. and Inestrosa, N.C. (2004). M1 muscarinic receptor activation protects neurons from beta-amyloid toxicity. A role for Wnt signaling pathway. Neurobiol Dis 17, 337-48.

[280]    Gomez-Ramos, A., Abad, X., Lopez Fanarraga, M., Bhat, R., Zabala, J.C. and Avila, J. (2004). Expression of an altered form of tau in Sf9 insect cells results in the assembly of polymers resembling Alzheimer's paired helical filaments. Brain Res 1007, 57-64.

[281]    Gonzalez-Billault, C., Jimenez-Mateos, E.M., Caceres, A., Diaz-Nido, J., Wandosell, F. and Avila, J. (2004). Microtubule-associated protein 1B function during normal development, regeneration, and pathological conditions in the nervous system. J Neurobiol 58, 48-59.

[282]    Hernandez, F., Cuadros, R. and Avila, J. (2004). Zeta 14-3-3 protein favours the formation of human tau fibrillar polymers. Neurosci Lett 357, 143-6.

[283]    Hernandez, F., Diaz-Hernandez, M., Avila, J. and Lucas, J.J. (2004). Testing the ubiquitin-proteasome hypothesis of neurodegeneration in vivo. Trends Neurosci 27, 66-9.

[284]    Hernandez, F., Perez, M., Lucas, J.J., Mata, A.M., Bhat, R. and Avila, J. (2004). Glycogen synthase kinase-3 plays a crucial role in tau exon 10 splicing and intranuclear distribution of SC35. Implications for Alzheimer's disease. J Biol Chem 279, 3801-6.

[285]    Moreno-Herrero, F., Perez, M., Baro, A.M. and Avila, J. (2004). Characterization by atomic force microscopy of Alzheimer paired helical filaments under physiological conditions. Biophys J 86, 517-25.

[286]    Salvador, L.M. et al. (2004). Neuronal microtubule-associated protein 2D is a dual a-kinase anchoring protein expressed in rat ovarian granulosa cells. J Biol Chem 279, 27621-32.

[287]    Sanchez, S., Jimenez, C., Carrera, A.C., Diaz-Nido, J., Avila, J. and Wandosell, F. (2004). A cAMP-activated pathway, including PKA and PI3K, regulates neuronal differentiation. Neurochem Int 44, 231-42.

[288]    Santa-Maria, I., Hernandez, F., Martin, C.P., Avila, J. and Moreno, F.J. (2004). Quinones facilitate the self-assembly of the phosphorylated tubulin binding region of tau into fibrillar polymers. Biochemistry 43, 2888-97.

[289]    Alvarez, D.E.L.A.R.M., Silva, I., Nilsen, J., Perez, M.M., Garcia-Segura, L.M., Avila, J. and Naftolin, F. (2005). Estradiol prevents neural tau hyperphosphorylation characteristic of Alzheimer's disease. Ann N Y Acad Sci 1052, 210-24.

[290]    Farias, G.G., Godoy, J.A., Vazquez, M.C., Adani, R., Meshulam, H., Avila, J., Amitai, G. and Inestrosa, N.C. (2005). The anti-inflammatory and cholinesterase inhibitor bifunctional compound IBU-PO protects from beta-amyloid neurotoxicity by acting on Wnt signaling components. Neurobiol Dis 18, 176-83.

[291]    Ferrer, I., Barrachina, M., Puig, B., Martinez de Lagran, M., Marti, E., Avila, J. and Dierssen, M. (2005). Constitutive Dyrk1A is abnormally expressed in Alzheimer disease, Down syndrome, Pick disease, and related transgenic models. Neurobiol Dis 20, 392-400.

[292]    Ferrer, I., Gomez-Isla, T., Puig, B., Freixes, M., Ribe, E., Dalfo, E. and Avila, J. (2005). Current advances on different kinases involved in tau phosphorylation, and implications in Alzheimer's disease and tauopathies. Curr Alzheimer Res 2, 3-18.

[293]    Gonzalez-Billault, C. et al. (2005). A role of MAP1B in Reelin-dependent neuronal migration. Cereb Cortex 15, 1134-45.

[294]    Hernandez, F., Engel, T., Gomez-Ramos, A., Perez, M. and Avila, J. (2005). Characterization of Alzheimer paired helical filaments by electron microscopy. Microsc Res Tech 67, 121-5.

[295]    Jimenez-Mateos, E.M., Paglini, G., Gonzalez-Billault, C., Caceres, A. and Avila, J. (2005). End binding protein-1 (EB1) complements microtubule-associated protein-1B during axonogenesis. J Neurosci Res 80, 350-9.

[296]    Jimenez-Mateos, E.M., Wandosell, F., Reiner, O., Avila, J. and Gonzalez-Billault, C. (2005). Binding of microtubule-associated protein 1B to LIS1 affects the interaction between dynein and LIS1. Biochem J 389, 333-41.

[297]    Kunjithapatham, R., Oliva, F.Y., Doshi, U., Perez, M., Avila, J. and Munoz, V. (2005). Role for the alpha-helix in aberrant protein aggregation. Biochemistry 44, 149-56.

[298]    Liu, Q. et al. (2005). Tau modifiers as therapeutic targets for Alzheimer's disease. Biochim Biophys Acta 1739, 211-5.

[299]    Liu, Q. et al. (2005). Alzheimer-specific epitopes of tau represent lipid peroxidation-induced conformations. Free Radic Biol Med 38, 746-54.

[300]    Mendieta, J. et al. (2005). Phosphorylation modulates the alpha-helical structure and polymerization of a peptide from the third tau microtubule-binding repeat. Biochim Biophys Acta 1721, 16-26.

[301]    Perez, M. et al. (2005). Characterization of a double (amyloid precursor protein-tau) transgenic: tau phosphorylation and aggregation. Neuroscience 130, 339-47.

[302]    Puig, B., Ferrer, I., Luduena, R.F. and Avila, J. (2005). BetaII-tubulin and phospho-tau aggregates in Alzheimer's disease and Pick's disease. J Alzheimers Dis 7, 213-20.

[303]    Ribe, E.M. et al. (2005). Accelerated amyloid deposition, neurofibrillary degeneration and neuronal loss in double mutant APP/tau transgenic mice. Neurobiol Dis 20, 814-22.

[304]    Ros, R. et al. (2005). A new mutation of the tau gene, G303V, in early-onset familial progressive supranuclear palsy. Arch Neurol 62, 1444-50.

[305]    Santa-Maria, I., Hernandez, F., Smith, M.A., Perry, G., Avila, J. and Moreno, F.J. (2005). Neurotoxic dopamine quinone facilitates the assembly of tau into fibrillar polymers. Mol Cell Biochem 278, 203-12.

[306]    Santa-Maria, I., Smith, M.A., Perry, G., Hernandez, F., Avila, J. and Moreno, F.J. (2005). Effect of quinones on microtubule polymerization: a link between oxidative stress and cytoskeletal alterations in Alzheimer's disease. Biochim Biophys Acta 1740, 472-80.

[307]    Smith, M.A., Nunomura, A., Lee, H.G., Zhu, X., Moreira, P.I., Avila, J. and Perry, G. (2005). Chronological primacy of oxidative stress in Alzheimer disease. Neurobiol Aging 26, 579-80.

[308]    Zhu, X., Lee, H.G., Casadesus, G., Avila, J., Drew, K., Perry, G. and Smith, M.A. (2005). Oxidative imbalance in Alzheimer's disease. Mol Neurobiol 31, 205-17.

[309]    Avila, J. (2006). Tau protein, the main component of paired helical filaments. J Alzheimers Dis 9, 171-5.

[310]    Avila, J. (2006). Tau phosphorylation and aggregation in Alzheimer's disease pathology. FEBS Lett 580, 2922-7.

[311]    Avila, J., Nitsch, R.M., Haass, C. and De Strooper, B. (2006). European Alzheimer disease funding. Nat Med 12, 776-7.

[312]    Doglio, L.E. et al. (2006). gamma-cleavage-independent functions of presenilin, nicastrin, and Aph-1 regulate cell-junction organization and prevent tau toxicity in vivo. Neuron 50, 359-75.

[313]    Engel, T., Goni-Oliver, P., Lucas, J.J., Avila, J. and Hernandez, F. (2006). Chronic lithium administration to FTDP-17 tau and GSK-3beta overexpressing mice prevents tau hyperphosphorylation and neurofibrillary tangle formation, but pre-formed neurofibrillary tangles do not revert. J Neurochem 99, 1445-55.

[314]    Engel, T., Hernandez, F., Avila, J. and Lucas, J.J. (2006). Full reversal of Alzheimer's disease-like phenotype in a mouse model with conditional overexpression of glycogen synthase kinase-3. J Neurosci 26, 5083-90.

[315]    Engel, T., Lucas, J.J., Gomez-Ramos, P., Moran, M.A., Avila, J. and Hernandez, F. (2006). Cooexpression of FTDP-17 tau and GSK-3beta in transgenic mice induce tau polymerization and neurodegeneration. Neurobiol Aging 27, 1258-68.

[316]    Gasic, G.P., Barco, A., Avila, J. and Lerma, J. (2006). A meeting to remember: meeting on memory and related disorders. EMBO Rep 7, 768-73.

[317]    Gomez-Ramos, A., Diaz-Hernandez, M., Cuadros, R., Hernandez, F. and Avila, J. (2006). Extracellular tau is toxic to neuronal cells. FEBS Lett 580, 4842-50.

[318]    Gomez-Ramos, A., Dominguez, J., Zafra, D., Corominola, H., Gomis, R., Guinovart, J.J. and Avila, J. (2006). Sodium tungstate decreases the phosphorylation of tau through GSK3 inactivation. J Neurosci Res 83, 264-73.

[319]    Gomez-Ramos, A., Dominguez, J., Zafra, D., Corominola, H., Gomis, R., Guinovart, J.J. and Avila, J. (2006). Inhibition of GSK3 dependent tau phosphorylation by metals. Curr Alzheimer Res 3, 123-7.

[320]    Jimenez-Mateos, E.M., Gonzalez-Billault, C., Dawson, H.N., Vitek, M.P. and Avila, J. (2006). Role of MAP1B in axonal retrograde transport of mitochondria. Biochem J 397, 53-9.

[321]    Moreno-Flores, M.T. et al. (2006). A clonal cell line from immortalized olfactory ensheathing glia promotes functional recovery in the injured spinal cord. Mol Ther 13, 598-608.

[322]    Pastrana, E., Moreno-Flores, M.T., Gurzov, E.N., Avila, J., Wandosell, F. and Diaz-Nido, J. (2006). Genes associated with adult axon regeneration promoted by olfactory ensheathing cells: a new role for matrix metalloproteinase 2. J Neurosci 26, 5347-59.

[323]    Quintana, C. et al. (2006). Study of the localization of iron, ferritin, and hemosiderin in Alzheimer's disease hippocampus by analytical microscopy at the subcellular level. J Struct Biol 153, 42-54.

[324]    Rubio, A., Avila, J. and Perez, M. (2006). Effect of acetylcholine on tau phosphorylation in human neuroblastoma cells. J Mol Neurosci 30, 185-8.

[325]    Rubio, A., Perez, M. and Avila, J. (2006). Acetylcholine receptors and tau phosphorylation. Curr Mol Med 6, 423-8.

[326]    Santa-Maria, I., Perez, M., Hernandez, F., Avila, J. and Moreno, F.J. (2006). Characteristics of the binding of thioflavin S to tau paired helical filaments. J Alzheimers Dis 9, 279-85.

[327]    Santa-Maria, I., Perez, M., Hernandez, F., Munoz, V., Moreno, F.J. and Avila, J. (2006). In vitro tau fibrillization: mapping protein regions. Biochim Biophys Acta 1762, 683-92.

[328]    Tortosa, E., Avila, J. and Perez, M. (2006). Acetylsalicylic acid decreases tau phosphorylation at serine 422. Neurosci Lett 396, 77-80.

[329]    Avila, J. (2007). Neuronal disorders: Introduction. Cell Mol Life Sci 64, 2191-2193.

[330]    Avila, J. and Hernandez, F. (2007). GSK-3 inhibitors for Alzheimer's disease. Expert Rev Neurother 7, 1527-33.

[331]    Engel, T., Lucas, J.J., Hernandez, F. and Avila, J. (2007). A mouse model to study tau pathology related with tau phosphorylation and assembly. J Neurol Sci 257, 250-4.

[332]    Gomez-Sintes, R., Hernandez, F., Bortolozzi, A., Artigas, F., Avila, J., Zaratin, P., Gotteland, J.P. and Lucas, J.J. (2007). Neuronal apoptosis and reversible motor deficit in dominant-negative GSK-3 conditional transgenic mice. Embo J 26, 2743-54.

[333]    Goni-Oliver, P., Lucas, J.J., Avila, J. and Hernandez, F. (2007). N-terminal cleavage of GSK-3 by calpain: a new form of GSK-3 regulation. J Biol Chem 282, 22406-13.

[334]    Hernandez, F. and Avila, J. (2007). Tauopathies. Cell Mol Life Sci 64, 2219-33.

[335]    Hirotani, S., Zhai, P., Tomita, H., Galeotti, J., Marquez, J. P., Gao, S., Hong, C., Yatani, A., Avila, J. and Sadoshima, J. (2007). Inhibition of glycogen synthase kinase 3beta during heart failure is protective. Circ Res 101, 1164-74.

[336]    Hooper, C. et al. (2007). Glycogen synthase kinase-3 inhibition is integral to long-term potentiation. Eur J Neurosci 25, 81-86.

[337]    Kortazar, D., Fanarraga, M.L., Carranza, G., Bellido, J., Villegas, J.C., Avila, J. and Zabala, J.C. (2007). Role of cofactors B (TBCB) and E (TBCE) in tubulin heterodimer dissociation. Exp Cell Res 313, 425-36.

[338]    Pastrana, E., Moreno-Flores, M.T., Avila, J., Wandosell, F., Minichiello, L. and Diaz-Nido, J. (2007). BDNF production by olfactory ensheathing cells contributes to axonal regeneration of cultured adult CNS neurons. Neurochem Int 50, 491-8.

[339]    Perez, M., Santa-Maria, I., Tortosa, E., Cuadros, R., Del Valle, M., Hernandez, F., Moreno, F.J. and Avila, J. (2007). The role of the VQIVYK peptide in tau protein phosphorylation. J Neurochem 103, 1447-60.

[340]    Rubio, A., Avila, J. and de Lecea, L. (2007). Cortistatin as a therapeutic target in inflammation. Expert Opin Ther Targets 11, 1-9.

[341]    Salcedo, M., Cuevas, C., Alonso, J.L., Otero, G., Faircloth, G., Fernandez-Sousa, J.M., Avila, J. and Wandosell, F. (2007). The marine sphingolipid-derived compound ES 285 triggers an atypical cell death pathway. Apoptosis 12, 395-409.

[342]    Santa-Maria, I., Hernandez, F., Del Rio, J., Moreno, F.J. and Avila, J. (2007). Tramiprosate, a drug of potential interest for the treatment of Alzheimer's disease, promotes an abnormal aggregation of tau. Mol Neurodegener 2, 17.

[343]    Santa-Maria, I., Hernandez, F., Moreno, F.J. and Avila, J. (2007). Taurine, an inducer for tau polymerization and a weak inhibitor for amyloid-beta-peptide aggregation. Neurosci Lett 429, 91-4.

[344]    Zhu, X., Avila, J., Perry, G. and Smith, M.A. (2007). Treating the lesions, not the disease. Am J Pathol 170, 1457-9.

[345]    Avila, J. (2008). Tau kinases and phosphatases. J Cell Mol Med 12, 258-9.

[346]    Avila, J., Soares, H., Fanarraga, M.L. and Zabala, J.C. (2008). Isolation of microtubules and microtubule proteins. Curr Protoc Cell Biol Chapter 3, Unit 3 29.

[347]    Bjorkdahl, C., Sjogren, M.J., Zhou, X., Concha, H., Avila, J., Winblad, B. and Pei, J.J. (2008). Small heat shock proteins Hsp27 or alphaB-crystallin and the protein components of neurofibrillary tangles: tau and neurofilaments. J Neurosci Res 86, 1343-52.

[348]    Engel, T., Goni-Oliver, P., Gomez de Barreda, E., Lucas, J.J., Hernandez, F. and Avila, J. (2008). Lithium, a potential protective drug in Alzheimer's disease. Neurodegener Dis 5, 247-9.

[349]    Engel, T., Goni-Oliver, P., Gomez-Ramos, P., Moran, M.A., Lucas, J.J., Avila, J. and Hernandez, F. (2008). Hippocampal neuronal subpopulations are differentially affected in double transgenic mice overexpressing frontotemporal dementia and parkinsonism linked to chromosome 17 tau and glycogen synthase kinase-3beta. Neuroscience 157, 772-80.

[350]    Gomez-Ramos, A., Diaz-Hernandez, M., Rubio, A., Miras-Portugal, M.T. and Avila, J. (2008). Extracellular tau promotes intracellular calcium increase through M1 and M3 muscarinic receptors in neuronal cells. Mol Cell Neurosci 37, 673-81.

[351]    Guerrero, R., Navarro, P., Gallego, E., Avila, J., de Yebenes, J.G. and Sanchez, M.P. (2008). Park2-null/tau transgenic mice reveal a functional relationship between parkin and tau. J Alzheimers Dis 13, 161-72.

[352]    Hernandez, F. and Avila, J. (2008). Tau aggregates and tau pathology. J Alzheimers Dis 14, 449-52.

[353]    Hernandez, F. and Avila, J. (2008). The role of glycogen synthase kinase 3 in the early stages of Alzheimers' disease. FEBS Lett 582, 3848-54.

[354]    Hernandez, F., Gomez-Ramos, A., Goni-Oliver, P., Avila, J. and Villanueva, N. (2008). Role of polyglycine repeats in the regulation of glycogen synthase kinase activity. Protein Pept Lett 15, 586-9.

[355]    Mondragon-Rodriguez, S. et al. (2008). Cleavage and conformational changes of tau protein follow phosphorylation during Alzheimer's disease. Int J Exp Pathol 89, 81-90.

[356]    Munoz-Fontela, C. et al. (2008). Induction of paclitaxel resistance by the Kaposi's sarcoma-associated herpesvirus latent protein LANA2. J Virol 82, 1518-25.

[357]    Navarro, P., Guerrero, R., Gallego, E., Avila, J., Luquin, R., Garcia Ruiz, P.J. and Sanchez, M.P. (2008). Motor alterations are reduced in mice lacking the PARK2 gene in the presence of a human FTDP-17 mutant form of four-repeat tau. J Neurol Sci 275, 139-44.

[358]    Navarro, P., Guerrero, R., Gallego, E., Avila, J., Luquin, R., Ruiz, P.J. and Sanchez, M.P. (2008). Memory and exploratory impairment in mice that lack the Park-2 gene and that over-express the human FTDP-17 mutant Tau. Behav Brain Res 189, 350-6.

[359]    Perez, M., Moran, M.A., Ferrer, I., Avila, J. and Gomez-Ramos, P. (2008). Phosphorylated tau in neuritic plaques of APP(sw)/Tau (vlw) transgenic mice and Alzheimer disease. Acta Neuropathol 116, 409-18.

[360]    Rubio, A., Perez, M., de Lecea, L. and Avila, J. (2008). Effect of cortistatin on tau phosphorylation at Ser262 site. J Neurosci Res 86, 2462-75.

[361]    Santa-Mara, I., Santpere, G., MacDonald, M.J., Gomez de Barreda, E., Hernandez, F., Moreno, F.J., Ferrer, I. and Avila, J. (2008). Coenzyme q induces tau aggregation, tau filaments, and Hirano bodies. J Neuropathol Exp Neurol 67, 428-34.

[362]    Santa-Maria, I., Cuadros, R., Moreno, F.J., Munoz, V., Avila, J. and Hernandez, F. (2008). Binding of tau protein to the ends of ex vivo paired helical filaments. J Alzheimers Dis 13, 177-85.

[363]    Utreras, E. et al. (2008). Microtubule-associated protein 1B interaction with tubulin tyrosine ligase contributes to the control of microtubule tyrosination. Dev Neurosci 30, 200-10.

[364]    Villoslada, P. et al. (2008). Immunotherapy for neurological diseases. Clin Immunol 128, 294-305.

[365]    Barrantes, A., Sotres, J., Hernando-Perez, M., Benitez, M.J., de Pablo, P.J., Baro, A.M., Avila, J. and Jimenez, J.S. (2009). Tau aggregation followed by atomic force microscopy and surface plasmon resonance, and single molecule tau-tau interaction probed by atomic force spectroscopy. J Alzheimers Dis 18, 141-51.

[366]    Berrocal, M., Marcos, D., Sepulveda, M.R., Perez, M., Avila, J. and Mata, A.M. (2009). Altered Ca2+ dependence of synaptosomal plasma membrane Ca2+-ATPase in human brain affected by Alzheimer's disease. Faseb J 23, 1826-34.

[367]    de Barreda, E.G. et al. (2009). Tau-knockout mice show reduced GSK3-induced hippocampal degeneration and learning deficits. Neurobiol Dis

[368]    Fuster-Matanzo, A., de Barreda, E.G., Dawson, H.N., Vitek, M.P., Avila, J. and Hernandez, F. (2009). Function of tau protein in adult newborn neurons. FEBS Lett

[369]    Garcia-Escudero, V. et al. (2009). Prevention of Senescence Progression in Reversibly Immortalized Human Ensheathing Glia Permits Their Survival After Deimmortalization. Mol Ther

[370]    Gomez-Ramos, A., Diaz-Hernandez, M., Rubio, A., Diaz-Hernandez, J.I., Miras-Portugal, M.T. and Avila, J. (2009). Characteristics and consequences of muscarinic receptor activation by tau protein. Eur Neuropsychopharmacol 19, 708-17.

[371]    Goni-Oliver, P., Avila, J. and Hernandez, F. (2009). Calpain-mediated truncation of GSK-3 in post-mortem brain samples. J Neurosci Res 87, 1156-61.

[372]    Goni-Oliver, P., Avila, J. and Hernandez, F. (2009). Memantine Inhibits Calpain-Mediated Truncation of GSK-3 Induced by NMDA: Implications in Alzheimer's Disease. J Alzheimers Dis

[373]    Guerrero, R., Navarro, P., Gallego, E., Garcia-Cabrero, A.M., Avila, J. and Sanchez, M.P. (2009). Hyperphosphorylated tau aggregates in the cortex and hippocampus of transgenic mice with mutant human FTDP-17 Tau and lacking the PARK2 gene. Acta Neuropathol 117, 159-68.

[374]    Hernandez, F., Barreda, E.G., Fustermatanzo, A., Olivergoni, P., Lucas, J.J. and Avila, J. (2009). The role of GSK3 in Alzheimer Disease. Brain Res Bull

[375]    Hernandez, F., Gomez de Barreda, E., Fuster-Matanzo, A., Lucas, J.J. and Avila, J. (2009). GSK3: A possible link between beta amyloid peptide and tau protein. Exp Neurol

[376]    Hernandez, F., Nido, J.D., Avila, J. and Villanueva, N. (2009). GSK3 Inhibitors and Disease. Mini Rev Med Chem 9, 1024-9.

[377]    Khachaturian, Z.S. et al. (2009). Creating a transatlantic research enterprise for preventing Alzheimer's disease. Alzheimers Dement 5, 361-6.

[378]    Lim, F. et al. (2009). Reversibly immortalized human olfactory ensheathing glia from an elderly donor maintain neuroregenerative capacity. Glia

[379]    Maurin, J.C., Couble, M.L., Staquet, M.J., Carrouel, F., About, I., Avila, J., Magloire, H. and Bleicher, F. (2009). Microtubule-associated protein 1b, a neuronal marker involved in odontoblast differentiation. J Endod 35, 992-6.

[380]    Perez, M. et al. (2009). Tau--an inhibitor of deacetylase HDAC6 function. J Neurochem 109, 1756-66.

[381]    Santa-Maria, I., Avila, J. and Rabano, A. (2009). Differential gene expression analysis of human entorhinal cortex support a possible role of some extracellular matrix proteins in the onset of Alzheimer disease. Neurosci Lett

[382]    Sereno, L. et al. (2009). A novel GSK-3beta inhibitor reduces Alzheimer's pathology and rescues neuronal loss in vivo. Neurobiol Dis 35, 359-67.

[383]    Simon, A.M. et al. (2009). Early Changes in Hippocampal Eph Receptors Precede the Onset of Memory Decline in Mouse Models of Alzheimer's Disease. J Alzheimers Dis

[384]    Tortosa, E., Santa-Maria, I., Moreno, F., Lim, F., Perez, M. and Avila, J. (2009). Binding of Hsp90 to Tau Promotes a Conformational Change and Aggregation of Tau Protein. J Alzheimers Dis

 

 

 


Premios

Premio Nacional de Biología “Santiago Ramón y Cajal”, 2004.

 

Toma de posesión del sillón nº 46 de la Real Academia de Ciencias Exactas, Físicas y Naturales, 2004.

 

 


Tesis doctorales

-          "Interacciones de proteínas contráctiles con el DNA". Victor G. Corces. Facultad de Ciencias. Universidad Autónoma de Madrid. Sobresaliente cum laude y Premio Extraordinario. 1979.
-          "Estructura y función de las proteínas asociadas al microtúbulo". Alfredo Villasante. Facultad de Ciencias. Universidad Autónoma de Madrid. Sobresaliente cum laude. 1981.
-          "Heterogeneidad estructural y funcional de isotubulinas de diferentes tejidos de porcino". José Carlos Díez. Facultad de Ciencias. Universidad Autónoma de Madrid. Sobresaliente cum laude. 1984.
-          "La proteína microtubular de Drosophila melanogaster". Francisco Wandosell. Universidad Autónoma de Madrid. Sobresaliente cum laude. 1984.
-          "Estructura y función del dímero de tubulina". Luís Serrano. Universidad Autónoma de Madrid. Sobresaliente cum laude. 1985.
-          "Caracterización y estudio de los dominios funcionales en la proteína asociada al microtúbulo MAP2". M.A. Hernández. Universidad Autónoma de Madrid. Sobresaliente cum laude. 1985.
-          "Caracterización de las proteínas asociadas al microtúbulo conocidas como factor tau". Esteban Montejo de Garcini. Universidad Autónoma de Madrid. Apto cum laude. 1986.
-          "Caracterización de la proteína MAP-1B de tejido nervioso. Identificación   de proteínas relacionadas en otros tejidos". Javier Díaz-Nido. Universidad Autónoma de Madrid. Apto cum laude. Noviembre 1988 y Premio         Extraordinario.
-          "Caracterización de proteínas centroméricas en células de mamífero". Leonor Kremer Barón. Universidad Autónoma de Madrid. Apto cum laude. Diciembre 1988.
-          "Caracterización de componentes estructurales y funcionales del centrosoma de células de mamífero". Jorge Domínguez Reyes. Universidad Autónoma de Madrid. Apto cum laude 1991 y Premio Extraordinario.
-          "Fosforilación de la proteína microtubular durante el proceso de extensión de las neuritas". Mar García Rocha. Universidad Autónoma de Madrid. Apto cum laude. Marzo 1993.
-          "Modificaciones postraduccionales de la proteína tau en la enfermedad de Alzheimer". Mª Dolores Ledesma. Universidad Autónoma de Madrid. Apto cum laude. Octubre 1995.
-          "Regulación de la fosforilación de MAP1B durante la diferenciación y regeneración axonal y su función en procesos de degeneración neurológica". Luis Ulloa. Universidad Autónoma de Madrid. Apto cum laude. Marzo 1995.
-          "Caracterización de la fosforilación de la proteína asociada a los microtubulos 2 (MAP2) en su región rica en prolina". Carlos Sánchez. Universidad Autónomade Madrid. Apto cum laude. Octubre 1997.
-          "Análisis funcional de la proteína asociada a microtubulos 1B. Aspectos celulares y moleculares". Christian González-Billault. Universidad Autónoma de Madrid. Sobresaliente cum laude. Noviembre 2000.
-          "La proteína tau: localización subcelular, interacción con nuevas proteínas y agregación patológica". Montserrat Arrasate. Universidad Autónoma de Madrid.Sobresaliente cum laude. Diciembre 2000.
-          “La proteína tau: fosforilación y ensamblaje”. Alberto Gómez. Universidad Autónoma de Madrid. Sobresaliente cum laude. Octubre 2004.
-          “Estudio funcional de la proteína asociada a microtúbulos MAP1B”. Eva-María Jiménez. Universidad Autónoma de Madrid. Sobresaliente cum laude. Julio 2005.
 

 

 



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