Monday, 18th December 2017

Molecular Neuropathology

    Tau function and dysfunction in Alzheimer disease






Jesús Avila










Research summary:

......  Fig01-300
  Retrovirus labeled granule neurons in the dentate gyrus of Alzheimer disease mouse model.
  Neuroblastoma cells overexpressing tau-GFP (green), stained with anti-EB1 (red). Although both proteins interact with microtubules, tau is a classical MAP that binds along the microtubule lattice, whereas EB1 is a +TIP that associates with microtubule "+" ends.

During years a main objective in our group has been the characterization of the function of the cytoskeletal proteins known as microtubule associated proteins (MAPs). One of these MAPs, MAP1B, is a protein that is mainly located at the axon, in neurons. Now, we have found that MAP1B plays an important role in the development of dendritic spines. On the other hand, we are mainly focusing our studies on other MAP, tau protein. Tau protein appears to play a role in Alzheimer disease and other dementias (tauopathies). Tau protein is a suitable substract for GSK3, a protein kinase also known as tau kinase 1 and that is also related to some features of Alzheimer disease. We have several works about tau and GSK3 and we have isolated, some years ago, a transgenic mouse that overexpresses GSK3. Now, using this mouse, we have studied the neurogenesis at the dentate gyrus. Our results have indicated a decrease in that neurogenesis, in the transgenic mouse, that results in degeneration of dentate gyrus. This degeneration is due to cell death but also to the indicated impaired neurogenesis. These features may be the cause of the memory deficits found in the transgenic mouse. Our actual studies will analyze if the memory impairment found in Alzheimer disease patients are also based in a deficient neurogenesis taking place at the dentate gyrus of the patients.


Relevant publications:

  • Barreda, E.G. and Ávila, J. (2011). Tau regulates the subcellular localization of calmodulin. Biochem Biophys Res Commun 408, 500-504.
  • Blazquez-Llorca, L., García-Marín, V., Merino-Serrais, P., Ávila, J. and Defelipe, J. (2011). Abnormal Tau Phosphorylation in the Thorny Excrescences of CA3 Hippocampal Neurons in Patients with Alzheimer's Disease. J Alzheimers Dis 26, 683-698.
  • Cantero, J.L., Moreno-López, B., Portillo, F., Rubio, A., Hita-Yanez, E. and Ávila, J. (2011). Role of tau protein on neocortical and hippocampal oscillatory patterns. Hippocampus 21, 827-834.
  • Del Barrio, L., Martín-de-Saavedra, M.D., Romero, A., Parada, E., Egea, J., Ávila, J., McIntosh, J.M., Wonnacott, S. and López, M.G. (2011). Neurotoxicity induced by okadaic acid in the human neuroblastoma SH-SY5Y line can be differentially prevented by alpha7 and beta2* nicotinic stimulation. Toxicol Sci 123, 193-205.
  • Fuster-Matanzo, A., Llorens-Martín, M., de Barreda, E.G., Ávila, J. and Hernández, F. (2011). Different Susceptibility to Neurodegeneration of Dorsal and Ventral Hippocampal Dentate Gyrus: A Study with Transgenic Mice Overexpressing GSK3beta. PLoS One 6, e27262


Doctoral Theses:

Elena Tortosa Binacua (2011). Estudio de la función de la proteína asociada a microtúbulos 1B durante el desarrollo neuronal. Universidad Autónoma de Madrid. Directores: María del Mar Pérez, Filip Lim y Laura Sayas.

Almudena Fuster Matanzo (2011). Estudio de la neurogénesis adulta en un modelo murino de sobreexpresión condicional de la glucógeno sintasa quinasa-3β. Universidad Autónoma de Madrid. Director: Félix Hernández.


Other Activities:

- Miembro del Comité organizador del Simposio internacional en Alzheimer y Parkinson (AD/PD), Barcelona 2011.
- Organización del congreso internacional en el año internacional del Alzheimer: "Global Alzheimer´s Research Summit", Madrid 2011.