Cai Yu, Yang Lu, Niu Fang, Liao Ke, Buch Shilpa
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, DRC 8024, Omaha, NE, 68198-5880, USA.
Adv Exp Med Biol. 2017;964:163-175. doi: 10.1007/978-3-319-50174-1_12.
Sigma-1 receptors (Sig-1R) are recognized as a unique class of non-G protein-coupled intracellular protein. Sig-1R binds to its ligand such as cocaine , resulting in dissociation of Sig-1R from mitochondrion-associated ER membrane (MAM) to the endoplasmic reticulum (ER), plasma membrane, and nuclear membrane, regulating function of various proteins. Sig-1R has diverse roles in both physiological as well as in pathogenic processes. The disruption of Sig-1R pathways has been implicated as causative mechanism(s) in the development of both neurodegenerative disorders such as Alzheimer disease (AD ), Parkinson disease (PD ), amyotrophic lateral sclerosis (ALS ) and Huntington Disease (HD ) . Additionally, the interaction of cocaine and Sig-1R has more recently been implicated in potentiating the pathogenesis of HIV-associated neurocognitive disorders (HAND) through impairment of blood-brain barrier (BBB), microglial activation and astrogliosis. On the other hand, restoration of Sig-1R homeostasis has been shown to exert neuroprotective effects. In this review, we provide an overview of how Sig-1R plays a role in the pathogenesis of neurodegenerative disorders and cocaine and implications for future development of therapeutic strategies.
西格玛-1受体（Sig-1R）被认为是一类独特的非G蛋白偶联的细胞内蛋白。Sig-1R与其配体如可卡因结合，导致Sig-1R从线粒体相关内质网膜（MAM）解离至内质网（ER）、质膜和核膜，从而调节各种蛋白质的功能。Sig-1R在生理过程和致病过程中都具有多种作用。Sig-1R通路的破坏被认为是神经退行性疾病如阿尔茨海默病（AD）、帕金森病（PD）、肌萎缩侧索硬化症（ALS）和亨廷顿病（HD）发病机制中的致病因素。此外，可卡因与Sig-1R的相互作用最近被认为通过损害血脑屏障（BBB）、小胶质细胞活化和星形胶质细胞增生，增强了HIV相关神经认知障碍（HAND）的发病机制。另一方面，Sig-1R内稳态的恢复已被证明具有神经保护作用。在这篇综述中，我们概述了Sig-1R在神经退行性疾病和可卡因发病机制中的作用以及对未来治疗策略发展的启示。
