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.
