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Culprit or Bystander: Defective Mitophagy in Alzheimer's Disease

Chenglong Xie1,2, Yahyah Aman2, Bryan A Adriaanse3

  • 1Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Frontiers in Cell and Developmental Biology
|February 4, 2020
PubMed

Insights

Impaired mitophagy, the cell's cleanup process for damaged mitochondria, is linked to Alzheimer's disease (AD) pathology. Targeting this process may offer a new therapeutic strategy for AD.

Area of Science:

  • Cellular Biology
  • Neuroscience
  • Mitochondrial Dynamics

Background:

  • Mitophagy is crucial for mitochondrial quality control, removing damaged mitochondria.
  • Accumulation of damaged mitochondria is observed in Alzheimer's disease (AD) brains.
  • Impaired mitophagy is implicated in AD pathogenesis across models and patient-derived cells.

Purpose of the Study:

  • To explore the role of impaired mitophagy in Alzheimer's disease.
  • To understand the relationship between mitophagy defects and AD hallmarks.
  • To assess the therapeutic potential of targeting mitophagy in AD.

Main Methods:

  • Review of studies on mitophagy in Alzheimer's disease animal models.
  • Analysis of data from AD patient-derived induced pluripotent stem cells (iPSC).
  • Examination of the interplay between mitophagy, amyloid-β, tau, and inflammation in AD.

Main Results:

  • Defective mitophagy contributes to damaged mitochondria accumulation in AD.
  • Vicious cycles exist between mitophagy defects and AD pathological hallmarks (amyloid-β, tau, inflammation).
  • The precise causal role of mitophagy defects in early AD remains challenging to ascertain due to model limitations.

Conclusions:

  • Impaired mitophagy is closely associated with Alzheimer's disease pathology.
  • Targeting mitophagy presents a promising therapeutic avenue for Alzheimer's disease.
  • Further research is needed to elucidate the causal relationship and optimize therapeutic strategies.
Keywords:
Alzheimer’s diseaseagingmemorymitophagyneuroprotection

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