Nicotinamide adenine dinucleotide glycohydrolase (NADase)

Nicotinamide adenine dinucleotide glycohydrolase (NADase) is an enzyme that catalyzes the hydrolysis of NAD+ to ADP-ribose and nicotinamide. In mammalian cells, CD38 is the principal NAD glycohydrolase, playing essential roles in controlling NAD+ levels, calcium signaling via degradation products, cell adhesion, and immune function. In pathogens such as Streptococcus pyogenes, NAD glycohydrolase acts as an intracellular toxin, depleting host cell NAD+ and promoting pathogen survival. NADase can be membrane-bound (GPI-anchored or transmembrane) and sometimes features additional functional domains. Its activity is implicated in aging, metabolic regulation, infection, cancer progression, and immune responses, making it a significant therapeutic target both for inhibition (in infectious and age-related diseases) and for targeted cell elimination (e.g., CD38-targeting antibodies in cancer).

Other names

NADaseNAD+ nucleosidaseDPNaseDPN hydrolaseNAD hydrolaseDiphosphopyridine nucleosidaseNicotinamide adenine dinucleotide nucleosidaseNAD nucleosidaseNicotinamide adenine dinucleotide glycohydrolaseCD38

CD38 antibodies: block NAD glycohydrolase activity, prevent NAD+ depletion, induce cell death in cancer cells expressing CD38. NADase inhibitors: prevent cleavage of NAD+, preserve NAD+ pools, protect host cells, and potentially reduce pathogen survival. Neutralization of bacterial NADase: inhibits pathogen-induced cell death in infectious disease.