Pharmacological Regulation of Mitophagy by Natural Plant Products as a Therapeutic Target for Alzheimer's Disease

ABSTRACT Alzheimer's disease (AD), a prevalent senile dementia, is characterized by the progressive decline in cognitive function, accumulation of tau tangles and Aβ plaques. Despite significant research efforts in the field of AD, effective therapeutic drugs for its prevention and treatment remain elusive. Consequently, a more comprehensive understanding of the molecular mechanisms underlying the pathological processes of AD is crucial for novel therapeutic strategies. Mitophagy, the selective degradation of mitochondria through autophagy, is an essential mechanism for maintaining mitochondrial homeostasis in terms of both quantity and quality. Mitophagy plays a crucial role in numerous cellular processes, including inflammation, differentiation, and apoptosis. Recent studies have increasingly demonstrated that mitophagy is extensively characterized in AD and may represent a novel therapeutic strategy for its treatment. Notably, a number of natural plant products (NPPs) have been demonstrated to modulate mitophagy and intervene in the pathological process of AD. For instance, NPPs such as urolithin A and β‐asarone have been reported to enhance mitophagy by activating the PINK1/Parkin pathway, thereby alleviating Aβ‐induced neurotoxicity. The distinctive multi‐target properties and favorable safety profiles of NPPs endow them with significant research potential and developmental value, establishing them as a vital resource for novel drug discovery. This review explores the mechanistic hypotheses linking mitophagy to AD pathology and provides a systematic overview of recent advances in representative NPPs that regulate mitophagy to alleviate AD‐related impairments, offering new perspectives for the development of therapeutic strategies against AD.