Sigma 1受体及其在神经系统疾病中的关键作用。

IF 4.9 Q1 CHEMISTRY, MEDICINAL ACS Pharmacology and Translational Science Pub Date : 2024-12-30 eCollection Date: 2025-01-10 DOI:10.1021/acsptsci.4c00564
Mustafa M Shokr, Ghada A Badawi, Shimaa M Elshazly, Hala F Zaki, Ahmed F Mohamed
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引用次数: 0

摘要

Sigma 1受体(S1R)是一种位于内质网(ER)膜上的多功能配体激活蛋白。它介导多种神经系统疾病,包括癫痫,肌萎缩侧索硬化症,阿尔茨海默病,亨廷顿病。S1R激动剂广泛的神经保护作用是通过多种促生存和抗凋亡的S1R介导的信号功能实现的。尽管如此,关于S1R活性的具体分子机制所知相对较少。许多关于S1R蛋白的研究强调了其通过控制内质网与线粒体之间的钙和脂质交换、内质网应激反应和许多其他机制来维持正常细胞稳态的重要性。在这篇综述中,我们将讨论S1R不同的细胞定位,并解释S1R相关的生物活性,如其在内质膜和线粒体相关内质膜界面的定位。在概述这些过程中涉及的细胞机制和重要结合伙伴的同时,我们也解释了这些途径的失调如何导致神经退行性疾病。
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Sigma 1 Receptor and Its Pivotal Role in Neurological Disorders.

Sigma 1 receptor (S1R) is a multifunctional, ligand-activated protein located in the membranes of the endoplasmic reticulum (ER). It mediates a variety of neurological disorders, including epilepsy, amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease. The wide neuroprotective effects of S1R agonists are achieved by a variety of pro-survival and antiapoptotic S1R-mediated signaling functions. Nonetheless, relatively little is known about the specific molecular mechanisms underlying S1R activity. Many studies on S1R protein have highlighted the importance of maintaining normal cellular homeostasis through its control of calcium and lipid exchange between the ER and mitochondria, ER-stress response, and many other mechanisms. In this review, we will discuss S1R different cellular localization and explain S1R-associated biological activity, such as its localization in the ER-plasma membrane and Mitochondrion-Associated ER Membrane interfaces. While outlining the cellular mechanisms and important binding partners involved in these processes, we also explained how the dysregulation of these pathways contributes to neurodegenerative disorders.

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来源期刊
ACS Pharmacology and Translational Science
ACS Pharmacology and Translational Science Medicine-Pharmacology (medical)
CiteScore
10.00
自引率
3.30%
发文量
133
期刊介绍: ACS Pharmacology & Translational Science publishes high quality, innovative, and impactful research across the broad spectrum of biological sciences, covering basic and molecular sciences through to translational preclinical studies. Clinical studies that address novel mechanisms of action, and methodological papers that provide innovation, and advance translation, will also be considered. We give priority to studies that fully integrate basic pharmacological and/or biochemical findings into physiological processes that have translational potential in a broad range of biomedical disciplines. Therefore, studies that employ a complementary blend of in vitro and in vivo systems are of particular interest to the journal. Nonetheless, all innovative and impactful research that has an articulated translational relevance will be considered. ACS Pharmacology & Translational Science does not publish research on biological extracts that have unknown concentration or unknown chemical composition. Authors are encouraged to use the pre-submission inquiry mechanism to ensure relevance and appropriateness of research.
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