Multifunctional roles of NAD⁺ and NADH in astrocytes.

The control and maintenance of the intracellular redox state is an essential task for cells and organisms. NAD(+) and NADH constitute a redox pair crucially involved in cellular metabolism as a cofactor for many dehydrogenases. In addition, NAD(+) is used as a substrate independent of its redox-carrier function by enzymes like poly(ADP)ribose polymerases, sirtuins and glycohydrolases like CD38. The activity of these enzymes affects the intracellular pool of NAD(+) and depends in turn on the availability of NAD(+). In addition, both NAD(+) and NADH as well as the NAD(+)/NADH redox ratio can modulate gene expression and Ca(2+) signals. Therefore, the NAD(+)/NADH redox state constitutes an important metabolic node involved in the control of many cellular events ranging from the regulation of metabolic fluxes to cell fate decisions and the control of cell death. This review summarizes the different functions of NAD(+) and NADH with a focus on astrocytes, a pivotal glial cell type contributing to brain metabolism and signaling.