Selective autophagy in the fight against neurodegeneration
Ana Maria Cuervo
Institute for Aging Studies, Albert Einstein College of Medicine, New York, USA
Cells count on surveillance systems to handle protein alterations and organelle damage. Malfunctioning of these systems occurs with age and is on the basis of different neurodegenerative conditions. Our studies have focused primarily on autophagy, degradation of proteins in lysosomes. We have found a double interplay whereby, different autophagic pathways contribute to clearance of pathogenic proteins but, conversely, these pathogenic proteins often became toxic for the autophagic system. Our current efforts are oriented to investigate the consequences of this toxicity on two selective forms of autophagy, chaperone-mediated autophagy (CMA) and in endosomal-microautophagy. We have developed conditional mouse models with modulatable CMA, where we have identified that decline on CMA activity contributes to neurodegeneration, increases proteotoxicity, accelerates the course of disease and facilitates propagation of the proteotoxic signature. We are currently utilizing genetic and chemical approaches to upregulate CMA in the neurodegenerative setting to determine the possible therapeutic value of such intervention.
Host: Olatz Pampliega