Mitochondrial dysfunction and oxidative stress are prominent features of a plethora of human disorders.
Dysregulation of mitochondrial functions represents a common pathogenic mechanism of diseases such as
neurodegenerative disorders and cancer. The maintenance of the Nicotinamide adenine dinucleotide (NAD+
) pool, and a
/NADH ratio, are essential for mitochondrial and cell functions. The synthesis and degradation of NAD+
transport of its key intermediates among cell compartments play an important role to maintain optimal NAD levels, for
regulation of NAD+
-utilizing enzymes, such as sirtuins (Sirt), poly-ADP-ribose polymerases, and CD38/157 enzymes, either
intracellularly as well as extracellularly. In this review, we present and discuss the links between NAD+
enzymes, mitochondria functions, and diseases. Attempts to treat various diseases with supplementation of NAD+
intermediates and inhibitors of sirtuins and ADP-ribosyl transferases may highlight a possible therapeutic approach for
therapy of cancer and neurodegenerative diseases.