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

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, arc 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.

Automated summary

Mitochondrial dysfunction and oxidative stress are common features in many human disorders, with NAD(+) playing a crucial role in maintaining mitochondrial and cell functions. Supplementing NAD(+) cycling intermediates and inhibiting sirtuins and ADP-ribosyl transferases may offer a potential therapeutic approach for treating cancer and neurodegenerative diseases.