title: NAD⁺/NADH metabolism and NAD⁺-dependent enzymes in cell death and ischemic brain injury: current advances and therapeutic implications.
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.
authors: Yingxin
authors: Y
authors: Ma
authors: Hui
authors: H
authors: Nie
authors: Heyu
authors: H
authors: Chen
authors: Jiefu
authors: J
authors: Li
authors: Yunyi
authors: Y
authors: Hong
authors: Ban
authors: B
authors: Wang
authors: Caixia
authors: C
authors: Wang
authors: Jie
authors: J
authors: Zhang
authors: Wei
authors: W
authors: Cao
authors: Mingchao
authors: M
authors: Zhang
authors: Yongning
authors: Y
authors: Xu
authors: Xianting
authors: X
authors: Ding
authors: Shan Kai
authors: SK
authors: Yin
authors: Xinkai
authors: X
authors: Qu
authors: School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, 1954 Hua Shan Road, Shanghai, 200032, P.R. China. weihaiy@sjtu.edu.cn.
authors: Weihai
authors: W
authors: Ying
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism*; D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism*; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism*; D016923:Cell Death; D006801:Humans; D009243:NAD / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D037761:Sirtuins / Q000378:metabolism*
chemical_list: D009243:NAD; D011065:Poly(ADP-ribose) Polymerases; D051997:ADP-ribosyl Cyclase 1; D037761:Sirtuins