Mitophagy in Alzheimer's disease and its potential as a therapeutic target

Accumulation of damaged mitochondria is a well-established hallmark of age-related neurodegenerative disorders, including Alzheimer's disease (AD). Increasing evidence suggests that mitophagy, a selective autophagic degradation of damaged mitochondria, plays an important role in AD progression. The interaction between mitophagy deficits and amyloid-β (Aβ) or Tau pathology may establish a vicious cycle that ultimately results in neuronal damage and death. Mitochondrial dysfunction exacerbates AD pathogenesis by activating the NLRP3 inflammasome, whereas modulation of mitophagy may confer neuroprotection by attenuating inflammation in neurons and microglia. Pathological ferroptosis has emerged as a potential key driver of AD, with mitophagy intriguingly demonstrating a dual role in this process. In this review, we elucidate the molecular mechanisms underlying mitophagy and its involvement in AD, thereby providing insights into AD pathogenesis. We further highlight the therapeutic potential of targeting mitophagy as a promising strategy for AD intervention.