Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (West), Mumbai, 400056, India.
Neurochem Res. 2023 Oct;48(10):2925-2935. doi: 10.1007/s11064-023-03960-6. Epub 2023 May 31.
Parkinson's disease is a neurodegenerative disease affecting mainly the elderly population. It is characterized by the loss of dopaminergic neurons of the substantia nigra pars compacta region. Parkinson's disease patients exhibit motor symptoms like tremors, rigidity, bradykinesia/hypokinesia, and non-motor symptoms like depression, cognitive decline, delusion, and pain. Major pathophysiological factors which contribute to neuron loss include excess/misfolded alpha-synuclein aggregates, microglial cell-mediated neuroinflammation, excitotoxicity, oxidative stress, and defective mitochondrial function. Sigma-1 receptors are molecular chaperones located at mitochondria-associated ER membrane. Their activation (by endogenous ligands or agonists) has shown neuroprotective and neurorestorative effects in various diseases. This review discusses the roles of activated Sig-1 receptors in modulating various pathophysiological features of Parkinson's disease like alpha-synuclein aggregates, neuroinflammation, excitotoxicity, and oxidative stress.
帕金森病是一种主要影响老年人群体的神经退行性疾病。它的特征是黑质致密部多巴胺能神经元的丧失。帕金森病患者表现出震颤、僵硬、运动迟缓/运动不能和运动症状，以及抑郁、认知能力下降、妄想和疼痛等非运动症状。导致神经元丧失的主要病理生理因素包括过量/错误折叠的α-突触核蛋白聚集、小胶质细胞介导的神经炎症、兴奋性毒性、氧化应激和线粒体功能缺陷。西格玛-1 受体是位于线粒体相关内质网膜上的分子伴侣。它们的激活（通过内源性配体或激动剂）已显示出在各种疾病中具有神经保护和神经修复作用。这篇综述讨论了激活的 Sig-1 受体在调节帕金森病的各种病理生理特征（如α-突触核蛋白聚集、神经炎症、兴奋性毒性和氧化应激）中的作用。
