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.