Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, 518055, China.
Curr Neuropharmacol. 2021;19(6):868-884. doi: 10.2174/1570159X18666200905143550.
Hydrogen sulfide (H2S) and hydrogen polysulfides are recognized as important signaling molecules that are generated physiologically in the body, including the central nervous system (CNS). Studies have shown that these two molecules are involved in cytoprotection against oxidative stress and inflammatory response. In the brain system, H2S and polysulfides exert multiple functions in both health and diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), memory decline, and glioma. Mechanistically, S-Persulfidation (also known as S-sulfuration or S-sulfhydration) of target proteins is believed to be a fundamental mechanism that underlies H2S-regulated signaling pathways. Cysteine S-Persulfidation is an important paradigm of post translational protein modification in the process of H2S signaling. This model is established as a critical redox mechanism to regulate numerous biological functions, especially in H2S-mediated neuroprotection and neurogenesis. Although the current research of S-Persulfidation is still in its infancy, accumulative evidence suggests that protein S-Persulfidation may share similar characteristics with protein S-nitrosylation. In this review, we will provide a comprehensive insight into the S-Persulfidation biology of H2S and polysulfides in neurological ailments and presume potential avenues for therapeutic development in these disorders based on S-Persulfidation of target proteins.
硫化氢 (H2S) 和多硫化氢被认为是在体内产生的重要信号分子，包括中枢神经系统 (CNS)。研究表明，这两种分子参与了对氧化应激和炎症反应的细胞保护。在脑系统中，H2S 和多硫化物在健康和疾病中都发挥着多种功能，包括阿尔茨海默病 (AD)、帕金森病 (PD)、亨廷顿病 (HD)、记忆衰退和神经胶质瘤。从机制上讲，靶蛋白的 S-过硫化（也称为 S-硫化或 S-巯基化）被认为是 H2S 调节信号通路的基本机制。半胱氨酸 S-过硫化是 H2S 信号转导过程中蛋白质翻译后修饰的重要范例。该模型的建立是一种关键的氧化还原机制，可调节众多生物学功能，尤其是在 H2S 介导的神经保护和神经发生中。尽管目前对半胱氨酸 S-过硫化的研究仍处于起步阶段，但越来越多的证据表明，蛋白质 S-过硫化可能与蛋白质 S-亚硝基化具有相似的特征。在这篇综述中，我们将全面了解 H2S 和多硫化物在神经疾病中的 S-过硫化生物学，并根据靶蛋白的 S-过硫化假设这些疾病潜在的治疗发展途径。
