NAD+ Degrading Enzymes, Evidence for Roles During Infection.

Arnold Tan,Craig L Doig

doi:10.3389/fmolb.2021.697359

Abstract

Declines in cellular nicotinamide adenine dinucleotide (NAD) contribute to metabolic dysfunction, increase susceptibility to disease, and occur as a result of pathogenic infection. The enzymatic cleavage of NAD+ transfers ADP-ribose (ADPr) to substrate proteins generating mono-ADP-ribose (MAR), poly-ADP-ribose (PAR) or O-acetyl-ADP-ribose (OAADPr). These important post-translational modifications have roles in both immune response activation and the advancement of infection. In particular, emergent data show viral infection stimulates activation of poly (ADP-ribose) polymerase (PARP) mediated NAD+ depletion and stimulates hydrolysis of existing ADP-ribosylation modifications. These studies are important for us to better understand the value of NAD+ maintenance upon the biology of infection. This review focuses specifically upon the NAD+ utilising enzymes, discusses existing knowledge surrounding their roles in infection, their NAD+ depletion capability and their influence within pathogenic infection.

Highlights

Fundamental to all cells, the pyridine nucleotide nicotinamide adenine dinucleotide (NAD) was initially identified as “cozymase” at the turn of the 20th Century
Activation of NAD+ degrading enzymes serve as a fundamental driver of NAD+ depletion
This is relevant in respect to poly (ADP-ribose) polymerase (PARP) and the cyclic ADP Ribose (cADPr) synthases as the physiological repercussions of their elevated activity in cells are welldocumented

Summary

Introduction

Fundamental to all cells, the pyridine nucleotide nicotinamide adenine dinucleotide (NAD) was initially identified as “cozymase” at the turn of the 20th Century. Studies have ascertained roles for SIRT-6 in the inflammatory response – Van gool et al demonstrated SIRT-6 activity exerted pro-inflammatory properties via the upregulation of TNF-α expression in murine bone marrow-derived dendritic cells, which was abolished upon the depletion of intracellular NAD+ or SIRT inhibition (Van Gool et al, 2009).

Results

Conclusion