基于PINK1/Parkin信号通路探讨中药复方及活性成分干预阿尔茨海默病的分子机制OA

The PTEN-induced putative kinase 1/Parkinson disease-associated proteins(PINK1/Parkin)signaling pathway plays a critical role in maintaining mitochondrial quality homeostasis by regulating mitophagy.Dysfunction of this pathway is closely associated with the pathogenesis and progression of Alzheimer's disease(AD),making it a potential therapeutic target.This review summarizes recent advances in understanding the mechanisms of the PINK1/Parkin pathway in AD and progress in understanding the modulation of this pathway by traditional Chinese medicine compounds and their active ingredients.Studies indicate that impaired PINK1/Parkin signaling leads to the accumulation of damaged mitochondria,thereby exacerbating amyloid β-protein(Aβ)deposition,Tau protein hyperphosphorylation,neuroinflammation,and oxidative stress.These processes create a vicious pathological cycle that drives the progression of AD.In terms of therapeutic intervention,tradiontional Chinese medicine can dynamically and bidirectionally modulate the PINK1/Parkin pathway by activating it to promote the clearance of damaged mitochondria and improve mitochondrial function,or by inhibiting its overactivation to maintain autophagic homeostasis and prevent excessive neuronal death.Furthermore,tradiontional Chinese medicine can alleviate oxidative stress,suppress neuroinflammation,intervene in Aβ and Tau pathologies,and activate upstream regulators such as SIRT1/3-FOXO3 and AMP-activated protein kinase,thereby forming a multitarget,holistic regulatory network.This review provides a deeper understanding of the pathological mechanisms of AD and serves as a reference for exploring tradiontional Chinese medicine-based therapeutic strategies targeting the PINK1/Parkin pathway.