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

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

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations


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
Issue number4
StatePublished - Apr 2022


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


Dive into the research topics of 'Pharmacological modulation of autophagy for Alzheimer's disease therapy: Opportunities and obstacles'. Together they form a unique fingerprint.

Cite this