Autophagy and parkinson’s disease

Jiahong Lu, Mingyue Wu, Zhenyu Yue

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

59 Scopus citations

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease characterized by motor system dysfunction. The etiology of PD has been linked with aging, environmental toxins and genetic mutation, while molecular pathogenesis of PD includes various factors, such as impaired protein homeostasis, oxidative stress, mitochondria dysfunction, synaptic transmission impairment, calcium homeostasis imbalance, prion-like α-synuclein transmission and neuron inflammation. Autophagy is a conserved bulk degradation process to maintain cellular homeostasis. Impairment of autophagy has been reported to be involved in the pathogenesis of PD. Coding proteins of several PD-related genes, such as SNCA, LRRK2, GBA, ATP13A2, VPS35 and FBXO7, are implicated in or affected by autophagy process. Furthermore, various pathogenic events during PD directly or indirectly interfere with the autophagy pathway, and dysregulation of autophagy has been observed in different neurotoxic PD models. Autophagy has been regarded as a potential therapeutic target for PD treatment. Indeed, modulations of autophagy-regulated genes (BECN1 and TFEB) expression exerted neuroprotection against PD models, and various autophagy regulators, such as rapamycin, trehalose, lysosome modulators and other small molecule autophagy inducers, have displayed neuroprotective effects in experimental PD models. Taken together, autophagy dysfunction has been implicated in the pathogenesis of PD, and pharmacological modulation of autophagy may be a new therapeutic strategy for the PD treatment.

Original languageEnglish
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer
Pages21-51
Number of pages31
DOIs
StatePublished - 2020

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1207
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

  • Autophagy
  • Parkinson disease
  • α-synuclein

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