The roles of S-nitrosylation and S-glutathionylation in Alzheimer's disease.

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.