对帕金森病产生神经保护的潜在新目标σ-1受体在做什么.docVIP

对帕金森病产生神经保护的潜在新目标：σ-1受体在做什么？ 帕金森病是一种与年龄相关的神经退行性疾病，主要特点是基底节多巴胺耗尽造成的典型运动功能紊乱，帕金森病的治疗旨在使用左旋多巴或多巴胺受体激动剂更换丢失的多巴胺。遗憾的是，到目前为止，所有经过测试的疾病修饰治疗均告失败，或者是因为它们没有达到主要终端，或者是因为尽管得到积极的结果但却无法起到神经保护作用。因此，必须寻找能够缓解疾病保护神经元不丢失的新型干预措施。 瑞典隆德大学Veronica Francardo教授的必威体育精装版研究指出，σ-1受体（SIG-1R）是一种分子伴侣蛋白，因其在几种疾病中的多种功能已吸引越来越多的关注。它位于线粒体相关内质网膜处，能够调节两种细胞器之间的钙信号。SIG-1R具有广泛表达能力，并能调动内源性防御机制以促进细胞存活。在细胞应激条件下，或在SIG-1R激动剂的药理学刺激下，这种蛋白可广泛地在细胞内支持各种功能，诸如脂质转运调节，突触信号调制，刺激再分配轴突和树突棘树枝状生长。在过去的几年里，一些研究报告显示了SIG-1R激动剂在阿尔茨海默病，肌萎缩性侧索硬化症和脑卒中动物模型中的神经保护性能。这些作用可通过多种机制归因于兴奋性毒性和细胞凋亡减少，如保护性基因衰减的上调，小胶质细胞激活的降低，活性氧簇和一氧化氮还原生成。相关研究内容发表在2014年11月第21期《中国神经再生研究（英文版）》杂志上。 SIG-1R的作用机制 Article: Sigma-1 receptor: a potential new target for Parkinson’s disease? by Veronica Francardo (Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, BMC F11, Lund University, Lund, Sweden) Francardo V. Sigma-1 receptor: a potential new target for Parkinson’s disease? Neural Regen Res. 2014;9(21):1882-1883. 欲获更多资讯： Sigma-1 receptor: a potential new target for Parkinson’s disease? Parkinson′s disease (PD) is an age-related neurodegenerative disorder characterized by typical motor signs and symptoms that are due to dopamine (DA) depletion in the basal ganglia. The treatment of PD is symptomatic, and aims at replacing the lost DA input using either L-DOPA or DA agonists. Pharmacological treatments able to interfere with the progressive neurodegenerative process of PD are the most critical unmet need. Unfortunately, all disease-modifying treatments tested so far have failed, either because they did not meet their primary endpoints or because a positive outcome could not be attributed to a neuroprotective effect. It is therefore essential to find new targets for disease-modifying interventions. A recently study by Prof. Veronica Francardo, Lund University, Sweden demonstrated that the Sigma-1 receptor (Sig-1R) is a chaperone protein that has been attracting increasing attention for its multiple functions and its implication in sever