NAD+/NADH metabolism and NAD+-dependent enzymes in cell death and ischemic brain injury: Current advances and therapeutic implications

Yingxin Ma, Hui Nie, Heyu Chen, Jiefu Li, Yunyi Hong, Ban Wang, Caixia Wang, Jie Zhang, Wei Cao, Mingchao Zhang, Yongning Xu, Xianting Ding, Shan Kai Yin, Xinkai Qu, Weihai Ying

Research output: Contribution to journalArticleResearchpeer-review

32 Citations (Scopus)

Abstract

NAD+ and NADH play crucial roles in a variety of biological processes including energy metabolism, mitochondrial functions, and gene expression. Multiple studies have indicated that NAD+ administration can profoundly decrease oxidative cell death as well as ischemic and traumatic brain injury, suggesting NAD+ metabolism as a promising therapeutic target for cerebral ischemia and head injury. Cumulating evidence has suggested that NAD+ can produce its protective effects by multiple mechanisms, including preventing mitochondrial alterations, enhancing energy metabolism, preventing virtually all forms of cell death including apoptosis, necrosis and autophagy, inhibiting inflammation, directly increasing antioxidation capacity of cells and tissues, and activating SIRT1. Increasing evidence has also suggested that NADH metabolism is a potential therapeutic target for treating several neurological disorders. A number of studies have further indicated that multiple NAD+-dependent enzymes such as sirtuins, polymerase(ADP-ribose) polymerases (PARPs) and CD38 mediate cell death and multiple biological processes. In this article, an overview of the recent findings regarding the roles of NAD+/NADH and NAD+- dependent enzymes in cell death and ischemic brain injury is provided. These findings have collectively indicated that NAD+/NADH and NAD+-dependent enzymes play fundamental roles in oxidative stress-induced cell death and ischemic brain injury, which may become promising therapeutic targets for brain ischemia and multiple other neurological disorders.

Original languageEnglish
Pages (from-to)1239-1247
Number of pages9
JournalCurrent Medicinal Chemistry
Volume22
Issue number10
DOIs
Publication statusPublished - 2015
Externally publishedYes

Keywords

  • CD38
  • Cell death
  • Ischemic brain injury
  • NAD+
  • Poly(ADP-ribose) polymerase
  • Sirtuins

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