脂滴-溶酶体轴在阿尔茨海默病中的作用机制及中药调控进展OA

Alzheimer's disease(AD)is a multifactorial neurodegenerative disorder whose pathological process involves interactions among lipid metabolism disorders,abnormal protein aggregation,and organelle dysfunction.Recent studies have revealed that lipid droplets and lysosomes do not function independently;instead,they form a functional coupling via the lipophagy pathway,which is defined in this paper as the"lipid droplet lysosome axis".This axis centers on lipid droplet surface proteins(PLIN2,DGAT2,Rab7)and lysosomal functional molecules(v-ATPase,LAMP2 A,cathepsins),achieving bidirectional regulation through membrane contact sites,material exchange,and the mTORC1-TFEB signaling feedback loop.Under AD pathology,dysregulation of this axis manifests as a vicious cycle in which abnormal lipid droplet accumulation and lysosomal dysfunction mutually exacerbate each other,thereby promoting Aβ deposition and tau phosphorylation.This review systematically elaborates the biological basis and dysregulation mechanisms of this axis,and based on this framework,constructs an"axis node-TCM component"mechanistic mapping.It summarizes evidence that active ingredients from traditional Chinese medicine,such as ginsenosides,restore axis function via nodes including TFEB,AMPK,and PPARα,and proposes research strategies and validation pathways for targeting this axis as a novel multi-target therapeutic approach for AD.