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Review Article

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

[ Vol. 28 , Issue. 41 ]


Palmiro Poltronieri*, Valeria Mezzolla, Ammad Ahmad Farooqi and Maria Di Girolamo   Pages 8453 - 8479 ( 27 )


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.


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


Institute of Sciences of Food Productions, National Research Council of Italy, via Monteroni km 7, 73100 Lecce, Division of Nephrology, Dialysis and Transplantation, Department of Emergency and Organ Transplantation, Aldo Moro University of Bari, Bari, Department of Molecular Oncology, Institute of Biomedical and Genetic Engineering (IBGE), Islamabad 44000, Sol & Pharma s.r.l. Biotechnology Research, 66030 Mozzagrogna

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