Autophagy and Parkinson’s Disease

Abstract

The defective clearance of misfolded or pathogenic proteins is a feature common to many neurodegenerative diseases, including Parkinson’s disease (PD). The autophagy-lysosome pathway (ALP) is a major cellular mechanism for maintaining proteostasis and is responsible for the degradation of aggregateprone proteins and defective organelles. As such, dysfunction of autophagy is a significant contributor to the pathogenesis of PD. This chapter contains an analysis of the literature linking autophagy to the etiology and progression of PD. Numerous PD-associated mutations have been identified that encode components or modulators of the ALP, revealing important insights into the pathogenic mechanisms underpinning dopaminergic neuronal cell death. In recent years, the study of neuroinflammation has also provided new insights into the mechanisms of cellular toxicity in neurodegeneration, with implications for PD research. The extensive links between ALP dysfunction, aging, and neurodegeneration have led to significant interest in the induction of autophagy as a potential therapy for neurodegenerative diseases, and so this chapter includes an evaluation of the potential for autophagy enhancers as PD therapeutics.