Roles of NAD+/NADH in Neurological Diseases

殷卫海

上海交通大学

Increasing evidence has indicated that NAD+ plays important roles in not only mitochondrial functions and energy metabolism, but also calcium homeostasis and inflammation.  It has also been found that NAD+ plays a key role in genotoxic agent-induced necrosis of neuronal and astrocyte cell death.  Our group has also found that intranasal administration of NAD+ can profoundly reduce ischemic brain damage.  Our latest study has indicated that NAD+, as well as NADH and NADPH, can selectively induce tumor cell death by increasing intracellular oxidative stress.  These observations have suggested that NAD+ may be used for treating not only cerebral ischemia, but also such neurological diseases as brain tumors.  However, many studies are warranted to further investigate the effects of NAD+ on normal neural cells and brain tumor cells.  Our recent studies have provided some new pieces of information regarding the mechanisms underlying the protective effects of NAD+.  For examples, we have found that NAD+ can prevent multiple mitochondrial toxin-induced apoptotic changes, in addition to its protective effects against oxidative stress-induced cell necrosis; and we also found that NAD+ treatment can markedly enhance intracellular ATP levels in cells exposed to oxidative stress.  Future studies are necessary to further investigate the roles of NAD+ metabolism and NAD+-dependent enzyme in brain ischemia and other neurological diseases, which may expose novel targets for treating the debilitating illnesses.