NAD Precursors, Mitochondria Targeting Compounds and ADP-Ribosylation Inhibitors in Treatment of Inflammatory Diseases and Cancer

Title:NAD Precursors, Mitochondria Targeting Compounds and ADP-Ribosylation Inhibitors in Treatment of Inflammatory Diseases and Cancer

Volume: 28 Issue: 41

Author(s): Palmiro Poltronieri*, Valeria Mezzolla, Ammad Ahmad Farooqi and Maria Di Girolamo

Affiliation:

• Institute of Sciences of Food Productions, National Research Council of Italy, Lecce, Italy

Keywords: ADP-ribosyl transferases, sirtuins, NAD cycling, nicotinamide, nicotinamide riboside, nicotinamide mononucleotide, compartmentalization.

Abstract: 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 positive NAD+/NADH ratio, are essential for mitochondrial and cell functions. The synthesis and degradation of NAD+ and transport of its key intermediates among cell compartments play an important role in maintaining optimal NAD levels, for the 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+, NAD+-consuming enzymes, mitochondria functions, and diseases. Attempts to treat various diseases with supplementation of NAD+ cycling intermediates and inhibitors of sirtuins and ADP-ribosyl transferases may highlight a possible therapeutic approach for therapy of cancer and neurodegenerative diseases.

Cite this article as:

Poltronieri Palmiro *, Mezzolla Valeria , Farooqi Ahmad Ammad and Di Girolamo Maria , NAD Precursors, Mitochondria Targeting Compounds and ADP-Ribosylation Inhibitors in Treatment of Inflammatory Diseases and Cancer, Current Medicinal Chemistry 2021; 28 (41) . https://dx.doi.org/10.2174/0929867328666210118152653