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

(E-pub Ahead of Print)

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

Journal Name: Current Medicinal Chemistry


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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 to maintain optimal NAD levels, for 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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Article Details

Published on: 18 January, 2021
(E-pub Ahead of Print)
DOI: 10.2174/0929867328666210118152653
Price: $95

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