Pharmacological modulation of autophagy for Alzheimer's disease therapy: Opportunities and obstacles

Zhiqiang Deng, Yu Dong, Xiaoting Zhou, Jia Hong Lu*, Zhenyu Yue*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

11 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is a prevalent and deleterious neurodegenerative disorder characterized by an irreversible and progressive impairment of cognitive abilities as well as the formation of amyloid β (Aβ) plaques and neurofibrillary tangles (NFTs) in the brain. By far, the precise mechanisms of AD are not fully understood and no interventions are available to effectively slow down progression of the disease. Autophagy is a conserved degradation pathway that is crucial to maintain cellular homeostasis by targeting damaged organelles, pathogens, and disease-prone protein aggregates to lysosome for degradation. Emerging evidence suggests dysfunctional autophagy clearance pathway as a potential cellular mechanism underlying the pathogenesis of AD in affected neurons. Here we summarize the current evidence for autophagy dysfunction in the pathophysiology of AD and discuss the role of autophagy in the regulation of AD-related protein degradation and neuroinflammation in neurons and glial cells. Finally, we review the autophagy modulators reported in the treatment of AD models and discuss the obstacles and opportunities for potential clinical application of the novel autophagy activators for AD therapy.

Original languageEnglish
Pages (from-to)1688-1706
Number of pages19
JournalActa Pharmaceutica Sinica B
Volume12
Issue number4
Early online date18 Dec 2021
DOIs
Publication statusPublished - Apr 2022
Externally publishedYes

Scopus Subject Areas

  • Pharmacology, Toxicology and Pharmaceutics(all)

User-Defined Keywords

  • Alzheimer's disease
  • Autophagy
  • Autophagy modulators
  • Genetic modulation
  • LC3-associated phagocytosis
  • Microglial autophagy
  • Neuroinflammation
  • Neuronal autophagy

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