AUTHOR=Chen Huiyi , Chen Feng , Jiang Ying , Zhang Lu , Hu Guizhen , Sun Furong , Zhang Miaoping , Ji Yao , Chen Yanting , Che Gang , Zhou Xu , Zhang Yu 

TITLE=A Review of ApoE4 Interference Targeting Mitophagy Molecular Pathways for Alzheimer's Disease

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 14 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.881239

DOI=10.3389/fnagi.2022.881239

ISSN=1663-4365

ABSTRACT=Alzheimer’s disease (AD) is one of the major worldwide causes of dementia that characterized 17
by irreversable learning decline, memory loss and behavior impairments. Mitophagy is a selective 18
autophagy through clearance of aberrant mitochondria for specifically degradation to maintain energy 19
generation, neuronal and synaptic function in brain. Accumulating evidence shows defective 20
mitophagy is believed as one of the early and prominent features in AD pathogenesis and draws 21
attention in recent years. APOE ε4 allele is the greatest genetic determinant for AD and is widely 22
reported to mediates detrimental effects on mitochondria function and mitophagic process. Given the 23
continuity of physiological process, this review takes mitochondrial dynamic and mitophagic core 24
events into consideration, highlights current knowledge about the molecular alterations from an 25
APOE-genotype perspective, synthesizes ApoE4-associated regulations and the cross talk between 26
these signaling, along with the focuses on general autophagic process and several pivotal processes of 27
mitophagy, including mitochondrial dynamic (DRP1, MFN-1), mitophagic induction (PINK1, 28
Parkin). These may shed new light on the link between ApoE4 and AD and provide novel insights for 29
promising mitophagy-targeted therapeutic strategies for AD.