Apelin/APJ系统对帕金森病模型的神经保护作用及机制研究进展

Research status on the neuroprotective efficacy and mechanism of Apelin/APJ system in Parkinson disease model

目前,帕金森病(PD)的发病机制仍不明确,也尚未有针对PD缓解的有效策略。越来越多的研究表明,自噬失调、线粒体损伤、内质网应激、氧化应激和过度神经炎症之间的复杂相互作用是PD发病机制的基础。Apelin是一种内源性神经肽,作为孤儿G蛋白偶联受体APJ的配体,可能通过抑制细胞凋亡和多巴胺能神经元丢失,增强自噬和抗氧化,抑制内质网应激及抑制过度神经炎症,起到神经保护作用,主要涉及PI3K/Akt/mTOR、ERK1/2和IRE1α/XBP1/CHOP等信号通路。笔者主要对Apelin/APJ轴在PD中的神经保护作用及机制研究进行综述。

The pathogenesis of Parkinson's disease(PD)is still unknown.There is still no effective disease-modifying strategy for PD,which is mostly managed symptomatically.A growing amount of preclinical evidence suggests the pathogenesis of PD is driven by a complex interaction of autophagy dysregulation,mitochondrial dysfunction,endoplasmic reticulum stress,oxidative stress,and excessive neuroinflammation.Emerging preclinical evidence suggests that Apelin,an endogenous neuropeptide that acts as a ligand of the orphan G protein-coupled receptor APJ,may play an important neuroprotective role in the pathogenesis of PD by inhibiting apoptosis and dopaminergic neuronal loss,enhancing autophagy and antioxidant effects suppressing,endoplasmic reticulum stress,and preventing excessive neuroinflammation,which mainly involves.PI3K/Akt/mTOR,ERK1/2,and IRE1/XBP1/CHOP and other signaling pathways involved.Given the growing preclinical evidence on the role of the Apelin/APJ axis in PD pathogenesis and the lack of a comprehensive review,we discuss the emerging role of the Apelin/APJ axis in PD pathophysiology and its great potential as a future therapeutic target in this article.