Autophagy Receptors and Neurodegenerative Diseases

Zhiqiang Deng, Kerry Purtell, Veronik Lachance, Mitchell S. Wold, Shi Chen, Zhenyu Yue

Research output: Contribution to journalReview articlepeer-review

134 Scopus citations

Abstract

Previously thought of as a nonselective digestion process, autophagy is now known to specifically degrade aggregated proteins and damaged cellular organelles through the action of autophagy receptors, which provides cellular quality control and maintains homeostasis. Autophagy receptors recognize and recruit specific cargoes to the autophagosome–lysosome pathway for degradation in ubiquitin-dependent and -independent manners, and their functions (in selective autophagy) are regulated by protein modifications, for example, phosphorylation and ubiquitination. Growing evidence has linked the genetic variants of autophagy receptors to neurodegenerative diseases and multiple experimental systems have validated their roles in modulating the disease process. Here, we review the recent advances in understanding the physiology and pathophysiology of autophagy receptors in selective autophagy, and discuss their potentials as therapeutic targets for neurodegenerative diseases. Autophagy receptors designate substrate specificity to autophagy through the recognition of specific cargo, such as aggregated proteins, damaged organelles and foreign pathogens. Accumulation of pathogenic proteins is a common feature of neurodegenerative disorders and dysfunctional autophagy is implicated in the disease state. Disease-associated mutations in autophagy receptors impair signaling in selective autophagy as well as aggregate clearance. Post-translational modification of autophagy receptors regulates the efficiency of aggregate clearance and presents a potential avenue for manipulating autophagy to treat neurodegenerative disease.

Original languageEnglish
Pages (from-to)491-504
Number of pages14
JournalTrends in Cell Biology
Volume27
Issue number7
DOIs
StatePublished - Jul 2017

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