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.