Novel Targets in Neurodegeneration and Neuroprotection

SCIENTIFIC AREA
Pathophysiology and Therapy of Neurological and Neuromuscular Diseases
CENTER
Instituto de Investigaciones Biomédicas “Alberto Sols” CSIC-UAM (IIBM)
VACANCIES
1
CONTACT E-MAIL
tiglesias@iib.uam.es
DESCRIPTION OF THE OFFER

Alzheimer´s disease (AD) is a neurodegenerative process characterized by gradually progressive memory loss. Synaptic alterations and the presence of dendritic spines with abnormal morphology are early features of this pathology. Hippocampal neurogenesis at the subgranular zone of the dentate gyrus is also impaired at initial stages of the disease. Later events include the accumulation of incorrectly folded proteins and the appearance of oxidative and inflammatory damage, increased synaptic dysfunction and neuronal death. The major neuropathological hallmarks of AD are extracellular accumulations of ß-amiloid plaques and the intracellular presence of neurofibrillar tangles enriched in hyperphosphorylated forms of the microtubules associated protein tau. Increases in GSK3-β kinase activity play a key role in the pathological accumulation of tau, causing inefficient clearance of damaged proteins mainly by deficits in degradative pathways mediated by the proteasome and autophagy. Since previous results from our group suggest that Kidins220 phosphorylation by GSK3-β and its accumulation might play a key role in AD etiopathology, we plan to investigate whether Kidins220 accumulation in AD is the cause or a consequence of this disease. To this end, and using cellular and animal models, we will determine the effects of modifying Kidins220 levels on several pathophysiological processes related with early or more advanced events in AD neurodegeneration, and the molecular mechanisms that modulate its proteostasis. We will use The identification of the mechanisms regulating the proteolysis of proteins as tau and Kidins220 might help to design strategies aiming at preventing their pathological accumulation.

MASTER
Biomolecules & Cell D.
Molecular Biomedicine
Biotechnology