Study of autophagy as the driving mechanism of neurodegenerative diseases

Abstract

It is believed that the loss of the protein quality control impairs the cellular events culminating in neurodegeneration. In view of this, the purpose of the present study is to evaluate the cellular quality control system in in vitro (primary cell culture) and in vivo (before the onset of neurodegeneration symptoms) models of sporadic (using rotenone) and familial neurodegenerative diseases such as Amyotrophic Lateral Sclerosis associated with SOD1 gene mutations, and Alzheimer's disease related to triplicated copies of important genes for this neurodegenerative disease using a mice model of Down syndrome. To this end, levels of proteins associated with activation of autophagy will be analyzed (including mitophagy), autophagy vesicles trafficking and autophagy flux will be also quantified. Additionally, it is intended to examine the role of BAG-2 protein (a co-chaperone that binds to the hsp70 to protein degradation) to modulate the autophagic activity before protein aggregation, as well as the role of physical activity on autophagy in the course of sporadic neurodegeneration as a therapeutic / preventive strategy. (AU)