Molecular mechanisms underlying exercise-enhanced autophagy in improving neuroplasticity in Alzheimer’s disease

作者：Qian Li, Renqing Zhao, Xin Tian, X. Xu · 发表于：Frontiers in Aging Neuroscience · 年份：2026 · DOI：10.3389/fnagi.2026.1780247 · 被引用次数：1 · 研究领域：Alzheimer's disease research and treatments、Autophagy in Disease and Therapy、Parkinson's Disease Mechanisms and Treatments

(Aβ) plaques due to abnormal protein aggregation, and intracellular accumulation of neurofibrillary tangles (NFTs) caused by hyperphosphorylation of tau proteins (p-Tau). These pathological changes induce synaptic loss and neuronal apoptosis, which leads to impaired neuroplasticity and progressive deterioration of cognitive function. Autophagy, a critical mechanism in the central nervous system (CNS) responsible for clearing misfolded protein aggregates and damaged organelles, plays a pivotal role in maintaining neuronal homeostasis and synaptic plasticity. However, AD is associated with autophagy impairment, resulting in the accumulation of toxic protein aggregates and damaged organelles. These pathological changes disrupt protein homeostasis, thereby exacerbating neurodegenerative processes. Currently, AD therapeutic strategies remain limited. Emerging evidence indicates that exercise intervention mitigates cognitive decline and enhances synaptic plasticity, potentially through reducing Aβ deposition and pathological phosphorylation of tau proteins. However, the precise mechanisms through which these interventions act remain to be fully elucidated. Recent studies have shown that exercise can promote autophagosome formation, fusion, and lysosomal hydrolytic function, thereby ameliorating the pathological progression of AD. Despite these promising findings, the precise molecular targets and underlying signaling mechanisms through which exercise modulates autophagy in AD remai...