Orai1-STIM1-TRPC1功能复合体在帕金森病中的研究进展

Recent advance in role of Orai1-STIM1-TRPC1 complete functional complex in Parkinson's disease

帕金森病(PD)是世界上第二常见的神经退行性疾病,它的发病机制与线粒体功能障碍、氧化应激反应以及钙稳态失衡有关。近年来,PD与Ca^(2+)的关系成为研究热点,钙稳态失衡可通过不同的途径导致PD。细胞内Ca^(2+)水平取决于钙库操纵性钙内流(SOCE),而SOCE由钙释放激活钙通道调节分子1(Orai1)、基质相互作用分子1(STIM1)及瞬时受体电位通道1(TRPC1)相互作用组成的功能复合体调节。常见的PD神经毒素可通过降低Orai1-STIM1-TRPC1复合体功能,损伤SOCE及其下游的信号通路选择性损伤多巴胺能神经元,并且Orai1-STIM1-TRPC1复合体可能通过作用于小胶质细胞以及内质网调控神经炎症、自噬现象以影响PD的发生发展。因此恢复Orai1-STIM1-TRPC1复合体表达及功能,维持钙稳态可能成为PD的有效治疗靶点。

Parkinson's disease is the second most common neurodegeneration,and its pathogenesis is related to mitochondrial dysfunction,oxidative stress and calcium homeostasis imbalance.In recent years,the relationship between Parkinson's disease and Ca^(2+) has become a research hotspot.Calcium homeostasis disorders can lead to Parkinson's disease in different ways.The level of intracellular calcium ion depends on store-operated calcium entry(SOCE),calcium release-activated calcium modulator1(Orai1),stromal interaction molecule 1(STIM1)and transient receptor potential channel 1(TRPC1)can form a functional complex to regulate it.PD neurotoxins can selectively damage dopaminergic neurons by reducing the function of Orai1-STIM1-TRPC1 complex and damaging SOCE and its downstream signal pathways.And the complex may affect the development of Parkinson's disease by acting on microglia and endoplasmic reticulum stress,and then regulate neuroinflammation and autophagy.Therefore,restoring the expression and function of Orai1-STIM1-TRPC1 function complex and maintaining calcium homeostasis may be the therapeutic targets of Parkinson's disease.