NAD⁺-Dependent Deacetylases and Medical Therapy

Deacetylases are a class of enzymes which remove the ?-. N-acetyl groups from lysine amino acids in histone and nonhistone targets. There are four classes of HDACs, with a distinct subgroup called sirtuins (HDAC class III) that rely on nicotinamide adenine dinucleotide (NAD) for their catalytic activity. The fact that most of the sirtuins require NAD for their deacetylase activity, indicates that they are major energy-sensing proteins in cells and tissues with the potency to effect a plethora of biochemical, physiological, and pathological processes. These effects exerted by various sirtuins are discussed in this chapter, as well as the processes regulating NAD levels by de novo and salvage pathways. Finally, we elaborate on current agents targeting sirtuins and salvage pathway enzymes and their preclinical and clinical outcomes.