基于Sigma-1受体的多靶点药物研究进展

Recent advances in multitarget-directed drugs based on Sigma-1 receptor

多靶点药物治疗针对疾病网络系统中的两个或多个相关靶点,同时调节疾病网络系统中的多个环节,从而发挥更好的临床疗效,具有更优越的安全性,现已在多种复杂疾病的治疗中开始应用。Sigma-1受体是一种独特的Ca^(2+)敏感伴侣蛋白,主要位于内质网和质膜中,在应激或病理条件下被激活,并通过作用于神经递质受体和离子通道受体等伴侣蛋白调节多种神经信号传导。近年来,研究发现基于Sigma-1受体的多靶点药物对神经痛、阿尔茨海默病、抑郁症、精神分裂症、帕金森病等具有良好的治疗效果,是开发神经系统疾病治疗药物的热门靶点。本文作者对近年来文献报道的Sigma-1受体多靶点药物进行综述,以期为基于Sigma-1受体多靶点药物的研发提供新的思路。

The Sigma-1 receptor is a unique Ca^(2+)-sensitive chaperone protein which mainly located in the endoplasmic reticulum and plasma membrane.It is activated under stress or pathological conditions and affects neurotransmission by interacting with different protein partners such as neurotransmitter receptors and ion channels.In recent years,multi-target drugs based on Sigma-1 receptor showed promising therapeutic potentials on neuropathic pain,Alzheimer's disease,depression,schizophrenia and Parkinson's disease,and the popular targets for the treatment of neurological diseases.In this review,recent advances in multitargetdirected drugs toward Sigma-1 receptor were reviewed,which could provide new ideas for the development of new drugs based on Sigma-1 receptor.