AGING-LINKED PROTEOSTASIS DECLINE: IMPLICATIONS FOR NEURODEGENERATIVE DISEASE

AbstractChaperones help proteins fold or send them to degradation, but they also regulate conformational protein cycles, protein-protein interactions, transcriptional programs, and buffer the many mutations present in the proteomes of individuals and cells in both normal and diseased states. The emerging understanding of protein homeostasis as an extraordinarily complex, multifaceted and nuanced actor in cellular regulation, calls for a better consideration of the machinery responsible for it, how it works under normal conditions, how it is regulated and how its impairment leads to disease. This can only occur through the integration of mechanistic, cell biological and genetic data with physiological studies of disease states. It is well-established that an impairment of protein homeostasis during aging underlies the onset of a whole set of neurodegenerative misfolding diseases. In this talk, I will discuss the tremendous therapeutic promise of protein homeostasis regulation in disease and aging.