Thursday, 21st June 2018

Molecular Neuropathology

      Molecular mechanism of neurodegeneration and regeneration


2016 12 14 Grupo F Wandosell 07


Francisco Wandosell




Research summary:

Our group, "Molecular mechanisms of Neurodegeneration and Regeneration ", is a line established in the CBM over several years. We are interested in the analysis of the molecular mechanisms fired by processes neurodegenerative, trying to understand the key points of these processes; for a second attempt to design new regenerative alternatives, or to propose new therapeutic targets.


First, our studies of molecular mechanisms of degeneration are focused on the role of Pi3K-Akt: GSK3 in neurodegeneration We have seen that some neuroprotective elements as estradiol modulates elements, such as GSK3 and β-catenin, proteins shared by other signaling pathways like Wnt. And we recently demonstrate that estradiol may trigger Akt-mTORC1 pathway. All these data represent a new signalling pathway, triggered by estradiol that would complement to IGF-1 and Wnt. These findings have led us to extend the analysis of signalling mediated by Estradiol in normal neuronal physiology and in some pathological conditions such as Ischemia model.

Second and complementary we are interested in the molecular mechanisms that regulate the generation and maintenance of the axonal polarity. This morphological polarity appears during development when the neuron differentiates and begins to extend an axon. Subsequently they "mature" and form their initial segment of the axon. Studies of several laboratories, including ours have shown that PI3K-kinase activity allows axonal growth and determining axonal polarity (in collaboration with JJ. Garrido´s group from Cajal Inst.). Our laboratory has helped identify some of the elements that control polarity, such that GSK3, control the polarity. Our work, in this field, will follow to identify upstream and downstream elements that would be essential for this "morphogenetic process".







In summary, we are focusing on track PI3K-Akt signalling and elements than those elements that control neuron morphogenesis and are modified in pathology.



    • ImmunoPEGliposome-mediated reduction of blood and brain amyloid levels in a mouse model of Alzheimer's disease is restricted to aged animals. Ordóñez-Gutiérrez L, Posado-Fernández A, Ahmadvand D, Lettiero B, Wu L, Antón M, Flores O, Moghimi SM, Wandosell F. Biomaterials. 2017 Jan;112:141-152.
    • WIP Drives Tumor Progression through YAP/TAZ-Dependent Autonomous Cell Growth. Gargini R, Escoll M, García E, García-Escudero R, Wandosell F, Antón IM. Cell Rep. 2016 Nov 15;17(8):1962-1977.
    • Class I PI3-kinase or Akt inhibition do not impair axonal polarization, but slow down axonal elongation. Diez H, Benitez MJ, Fernandez S, Torres-Aleman I, Garrido JJ, Wandosell F. Biochim Biophys Acta. 2016 Nov;1863(11):2574-2583.
    • AβPP/PS1 Transgenic Mice Show Sex Differences in the Cerebellum Associated with Aging. Ordoñez-Gutierrez L, Fernandez-Perez I, Herrera JL, Anton M, Benito-Cuesta I, Wandosell F. J Alzheimers Dis. 2016 Sep 6;54(2):645-56.
    • Secreted herpes simplex virus-2 glycoprotein G alters thermal pain sensitivity by modifying NGF effects on TRPV1. Cabrera JR, Viejo-Borbolla A, Alcamí A, Wandosell F. J Neuroinflammation. 2016 Aug 30;13(1):210.
    • Reticulon-4B/Nogo-B acts as a molecular linker between microtubules and actin cytoskeleton in vascular smooth muscle cells. Rodríguez-Feo JA, Gallego-Delgado J, Puerto M, Wandosell F, Osende J. Biochim Biophys Acta. 2016 Aug;1863(8):1985-95.
    • Angiotensin II type-2 receptor stimulation induces neuronal VEGF synthesis after cerebral ischemia. Mateos L, Perez-Alvarez MJ, Wandosell F.
    • Biochim Biophys Acta. 2016 Jul;1862(7):1297-308.
    • Oncogene-mediated tumor transformation sensitizes cells to autophagy induction. Gargini R, García-Escudero V, Izquierdo M, Wandosell F. Oncol Rep. 2016 Jun;35(6):3689-95.
    • PTEN recruitment controls synaptic and cognitive function in Alzheimer's models. Knafo S, Sánchez-Puelles C, Palomer E, Delgado I, Draffin JE, Mingo J, Wahle T, Kaleka K, Mou L, Pereda-Perez I, Klosi E, Faber EB, Chapman HM, Lozano-Montes L, Ortega-Molina A, Ordóñez-Gutiérrez L, Wandosell F, Viña J, Dotti CG, Hall RA, Pulido R, Gerges NZ, Chan AM, Spaller MR, Serrano M, Venero C, Esteban JA. Nat Neurosci. 2016 Mar;19(3):443-53.
    • Stroke and Neuroinflamation: Role of Sexual Hormones. Perez-Alvarez MJ, Wandosell F. Curr Pharm Des. 2016;22(10):1334-49. 
    • The hunt for brain Aβ oligomers by peripherally circulating multi-functional nanoparticles: Potential therapeutic approach for Alzheimer disease. Mancini S, Minniti S, Gregori M, Sancini G, Cagnotto A, Couraud PO, Ordóñez-Gutiérrez L, Wandosell F, Salmona M, Re F. Nanomedicine. 2016 Jan;12(1):43-52

Other activities:

- Master in Genetic and Cellular Biology (UAM and UAH ). Drª. Rosa Sacedon y Drª Marta Torroba. Department of Cellular Biology. UCM

- Master in Molecular and Cellular Biology. Department of Molecular Biology and Department of Biochemistry. UAM. Drª. Inés Antón (CNB) and Drª . Margarita Cervera (UAM)

- Master in Molecular Biomedicine. Department of Molecular Biology and Biochemistry (UAM). Dr. Javier Díaz Nido (Dpt. Molecular Biology, UAM) and Dr. Francisco Wandosell (CBMSO, CSIC-UAM).

This group is also part of the Centre for biomedical research in neurodegenerative diseases network (CiberNed):

Industry collaboration:
- Allinky S. L. (2015-2016)

Doctoral theses:

Maribel Escoll (2015).