Dyer Ryan R, Ford Katarena I, Robinson Renã A S
Department of Chemistry, Vanderbilt University, Nashville, TN, United States.
Department of Chemistry, Vanderbilt University, Nashville, TN, United States; Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United States; Vanderbilt Memory & Alzheimer's Center, Nashville, TN, United States; Vanderbilt Institute of Chemical Biology, Nashville, TN, United States; Vanderbilt Brain Institute, Nashville, TN, United States.
Methods Enzymol. 2019;626:499-538. doi: 10.1016/bs.mie.2019.08.004.
Alzheimer's disease (AD) is a debilitating dementia with complex pathophysiological alterations including modifications to endogenous cysteine. S-nitrosylation (SNO) is a well-studied posttranslational modification (PTM) in the context of AD while S-glutathionylation (PSSG) remains less studied. Excess reactive oxygen and reactive nitrogen species (ROS/RNS) directly or indirectly generate SNO and PSSG. SNO is dysregulated in AD and plays a pervasive role in processes such as protein function, cell signaling, metabolism, and apoptosis. Despite some studies into the role of SNO in AD, multiple identified SNO proteins lack deep investigation and SNO modifications outside of brain tissues are limited, leaving the full role of SNO in AD to be elucidated. PSSG homeostasis is perturbed in AD and may affect a myriad of cellular processes. Here we overview the role of nitric oxide (NO) in AD, discuss proteomic methodologies to investigate SNO and PSSG, and review SNO and PSSG in AD. A more thorough understanding of SNO, PSSG, and other cysteinyl PTMs in AD will be helpful for the development of novel therapeutics against neurodegenerative diseases.
阿尔茨海默病（AD）是一种使人衰弱的痴呆症，具有复杂的病理生理改变，包括内源性半胱氨酸的修饰。在AD背景下，S-亚硝基化（SNO）是一种研究充分的翻译后修饰（PTM），而S-谷胱甘肽化（PSSG）的研究较少。过量的活性氧和活性氮物质（ROS/RNS）直接或间接产生SNO和PSSG。SNO在AD中失调，并在蛋白质功能、细胞信号传导、代谢和细胞凋亡等过程中发挥普遍作用。尽管对SNO在AD中的作用进行了一些研究，但多个已鉴定的SNO蛋白缺乏深入研究，且脑组织外的SNO修饰有限，SNO在AD中的完整作用仍有待阐明。PSSG稳态在AD中受到干扰，可能影响众多细胞过程。在此，我们概述一氧化氮（NO）在AD中的作用，讨论研究SNO和PSSG的蛋白质组学方法，并综述AD中的SNO和PSSG。更全面地了解AD中的SNO、PSSG和其他半胱氨酸翻译后修饰将有助于开发针对神经退行性疾病的新型疗法。
