The importance of pharmacological modulation of the enzymatic activity of CD38 and intracellular NAD levels

Abstract

CD38 may play important roles in the pathophysiology of different human diseases, like obesity, diabetes, chronic lymphocyte leukemia and other disease either through the enzymatic or receptorial functions. Also, it has a role in energy homeostasis, signal transduction, and aging. Interestingly, CD38 is a major regulator of intracellular nicotinamide adinin dinucleotide (NAD+) levels. It is the main NADase enzyme, it uses NAD to produce the main calcium mobilizing messengers. On the other hand, NAD is a key molecule that is involved in multiple signaling pathways and metabolic conditions. Thus, it is of highly importance to regulate of CD38 catalytic activity. Therefore, it is of interest to many investigators to find inhibitors of CD38 function to verify CD38 as a new potential therapeutic target. Here we draw attention to the importance of CD38 catalytic function and its involvement in several disease. In addition to the importance of intracellular NAD, the main NAD-consuming enzymes, and biosynthesis enzymes. The main regulators of CD38 activity (inhibitors or activators) are also reported to provide a theoretical basis for further drug design.This review is aimed at giving a brief insight into the progress made to date about CD38/NAD relationship. CD38/NAD link plays important roles in signaling pathways that may contribute to human pathologies, it is a potential target for drug development.