Sigma-1受体在神经退行性疾病中的角色
首发时间:2020-06-24
摘要:神经退行性疾病是一类主要影响机体运动神经元的疾病,常见的如老年痴呆、肌萎缩侧索硬化症等,这类疾病给患者、家庭及社会带来了很大影响和负担,研发出合理有效的治疗手段一直是一个难题。Sigma-1受体是一个非阿片类、非G蛋白偶联类的小分子受体蛋白,在神经系统中表达量丰富,在细胞中主要定位在线粒体与内质网的连接区域,参与调控多种重要的细胞信号通路,影响细胞存活。有研究报道Sigma-1受体的多种突变与神经退行性疾病的发病相关,其中E102Q突变会导致少年型肌萎缩侧索硬化症。在神经退行性疾病的动物模型中该受体的缺失会加重疾病的症状。另外,该受体的激动剂被证明具有神经保护作用。在本文中,我们以ALS为例对神经退行性疾病进行了简单介绍,并对Sigma-1受体的功能及其突变可能的致病机理进行了综述,希望对神经退行性疾病的治疗研究有所启发和帮助。
关键词: 分子生物学 Sigma-1受体 神经退行性疾病 肌萎缩侧索硬化症
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Role of Sigma-1 Receptor in Neurodegenerative Diseases
Abstract:Neurodegenerative diseases are a type of diseases that mainly affect the neurons, such as dementia, amyotrophic lateral sclerosis, etc. Such diseases have brought great impact and burden to patients, families and the society, and it has always been a difficult problem to develop reasonable and effective treatments. Sigma-1 receptor is a non-opioid and non-G protein-coupled small molecule receptor which is abundantly expressed in the nervous system. It predominantly resides in the endoplasmic reticulum (ER), especially ER sub-region contacting mitochondria, namely the mitochondrial-associated membrane (MAM) in cell, and participates in a variety of important cell signaling pathways that affect cell survival. There are reports that multiple mutations of the Sigma-1 receptor are associated with the onset of neurodegenerative diseases. E102Q, as one of those mutations can cause juvenile amyotrophic lateral sclerosis. The absence of this receptor in animal models of neurodegenerative diseases can also aggravate the symptoms of the disease. In addition, agonists of this receptor have been shown to have neuroprotective effects. In this paper, we have introduced neurodegenerative diseases, mainly ALS and reviewed the function of Sigma-1 receptor and the possible pathogenic mechanism of its mutations, hoping to help and inspire the research and treatment of neurodegenerative diseases.
Keywords: Molecular Biology Sigma-1 Receptor Neurodegenrative Disease Amyotrophic Lateral Sclerosis
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Sigma-1受体在神经退行性疾病中的角色
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