Dissecting the Autophagic-Lysosomal Pathway in Neurodegeneration and Risk Factors that Promote Proteinopathy

Protein quality control efficiency is critical for continued brain function and macroautophagy is a major pathway involved in the clearance of proteins and lipids, including the removal of protein aggregates and dysfunctional organelles. Understanding the molecular and biochemical underpinnings of how protein (and lipid) turnover is altered in aging and neurodegenerative diseases of aging (NDA), like AD, is critical to address the potential health impact. Further, all NDAs are in part characterized by protein aggregation, indicating the widespread importance of protein quality control in the brain. Today’s discussion will explore the role of proteostasis in NDAs and how pathology can spread between regions. The presentation will explore components of autophagic flux and how they may be disrupted in NDAs. Importantly, understanding these changes is critical for the design of therapeutics targeting autophagic flux, as well as the implementation of early biomarker of disease to improve clinical outcome. Changes in proteostasis are also related to the how risk factors of NDAs can impact the brain, and this will be explored as well as gaps in understanding the etiology of Alzheimer’s disease.