TY - JOUR
T1 - NAD+/NADH metabolism and NAD+-dependent enzymes in cell death and ischemic brain injury
T2 - Current advances and therapeutic implications
AU - Ma, Yingxin
AU - Nie, Hui
AU - Chen, Heyu
AU - Li, Jiefu
AU - Hong, Yunyi
AU - Wang, Ban
AU - Wang, Caixia
AU - Zhang, Jie
AU - Cao, Wei
AU - Zhang, Mingchao
AU - Xu, Yongning
AU - Ding, Xianting
AU - Yin, Shan Kai
AU - Qu, Xinkai
AU - Ying, Weihai
N1 - Publisher Copyright:
© 2015 Bentham Science Publishers.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - CD38
KW - Cell death
KW - Ischemic brain injury
KW - NAD+
KW - Poly(ADP-ribose) polymerase
KW - Sirtuins
UR - http://www.scopus.com/inward/record.url?scp=84931261503&partnerID=8YFLogxK
U2 - 10.2174/0929867322666150209154420
DO - 10.2174/0929867322666150209154420
M3 - Article
C2 - 25666794
AN - SCOPUS:84931261503
SN - 0929-8673
VL - 22
SP - 1239
EP - 1247
JO - Current Medicinal Chemistry
JF - Current Medicinal Chemistry
IS - 10
ER -