Unraveling the Connection Between ApoE4 and Alzheimer’s Through Mitophagy

Published on May 20, 2022

Imagine a bustling city with well-functioning waste management systems that keep the streets clean. In our bodies, a similar process called mitophagy ensures that dysfunctional mitochondria are cleared out, maintaining a healthy brain. However, scientists have discovered that defective mitophagy plays a crucial role in the early stages of Alzheimer’s disease (AD). One of the major genetic factors linked to AD is the APOE ε4 allele, which not only affects mitochondria function but also interferes with the mitophagic process. This comprehensive review explores the molecular mechanisms behind this connection, focusing on the effects of ApoE4 on mitochondrial dynamics and key players in mitophagy. By understanding these intricate pathways, researchers hope to develop targeted therapeutic strategies for AD that revitalize the process of mitophagy and protect neuronal health. To dive deeper into this fascinating research, check out the full article!

Alzheimer’s disease (AD) is one of the major worldwide causes of dementia that is characterized by irreversible decline in learning, memory loss, and behavioral impairments. Mitophagy is selective autophagy through the clearance of aberrant mitochondria, specifically for degradation to maintain energy generation and neuronal and synaptic function in the brain. Accumulating evidence shows that defective mitophagy is believed to be as one of the early and prominent features in AD pathogenesis and has drawn attention in the recent few years. APOE ε4 allele is the greatest genetic determinant for AD and is widely reported to mediate detrimental effects on mitochondria function and mitophagic process. Given the continuity of the physiological process, this review takes the mitochondrial dynamic and mitophagic core events into consideration, which highlights the current knowledge about the molecular alterations from an APOE-genotype perspective, synthesizes ApoE4-associated regulations, and the cross-talk between these signaling, along with the focuses on general autophagic process and several pivotal processes of mitophagy, including mitochondrial dynamic (DRP1, MFN-1), mitophagic induction (PINK1, Parkin). These may shed new light on the link between ApoE4 and AD and provide novel insights for promising mitophagy-targeted therapeutic strategies for AD.

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