Mono(ADP-ribosyl)ation Enzymes and NAD Metabolism: A Focus on Diseases and Therapeutic Perspectives.

Mono(ADP-ribose) transferases and mono(ADP-ribosyl)ating sirtuins use NAD to perform the mono(ADP-ribosyl)ation, a simple form of post-translational modification of proteins and, in some cases, of nucleic acids. The availability of NAD is a limiting step and an essential requisite for NAD consuming enzymes. The synthesis and degradation of NAD, as well as the transport of its key intermediates among cell compartments, play a vital role in the maintenance of optimal NAD levels, which are essential for the regulation of NAD-utilizing enzymes. In this review, we provide an overview of the current knowledge of NAD metabolism, highlighting the functional liaison with mono(ADP-ribosyl)ating enzymes, such as the well-known ARTD10 (also named PARP10), SIRT6, and SIRT7. To this aim, we discuss the link of these enzymes with NAD metabolism and chronic diseases, such as cancer, degenerative disorders and aging.