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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

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

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

Volume 28, Issue 41, 2021

Published on: 18 January, 2021

Page: [8453 - 8479] Pages: 27

DOI: 10.2174/0929867328666210118152653

Price: $65


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.

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

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