Roles of NAD(+) / NADH and NADP(+) / NADPH in cell death.

A rapidly growing body of information has suggested that NAD (including NAD+ and NADH) and NADP (including NADP+ and NADPH) could be new fundamental factors in cell death: Many studies have indicated key roles of poly (ADP-ribose) polymerases and sirtuins--two families of NAD-dependent enzymes--in cell death; and NAD may also affect cell survival by influencing mitochondrial permeability transition, apoptosis-inducing factor and GAPDH. NAD may further influence cell survival by its effects on calcium homeostasis, gene expression and immunological functions. Due to the crucial roles of oxidative stress in cell death, NADPH may mediate cell death by its major effects on oxidative stress: NADPH is a key factor in cellular antioxidation systems; and NADPH oxidase is also a major generator of oxidative stress. With growing information about the novel biological properties of NAD and NADP, it is likely that new roles of NAD and NADP in cell death and various diseases will be elucidated. The elucidation may not only improve our understanding about the fundamental mechanisms of cell death, but also suggest new therapeutic targets for a variety of diseases.