Exploring NAD+ metabolism in host-pathogen interactions

Cell Mol Life Sci. 2016 Mar;73(6):1225-36. doi: 10.1007/s00018-015-2119-4. Epub 2015 Dec 30.

Abstract

Nicotinamide adenine dinucleotide (NAD(+)) is a vital molecule found in all living cells. NAD(+) intracellular levels are dictated by its synthesis, using the de novo and/or salvage pathway, and through its catabolic use as co-enzyme or co-substrate. The regulation of NAD(+) metabolism has proven to be an adequate drug target for several diseases, including cancer, neurodegenerative or inflammatory diseases. Increasing interest has been given to NAD(+) metabolism during innate and adaptive immune responses suggesting that its modulation could also be relevant during host-pathogen interactions. While the maintenance of NAD(+) homeostatic levels assures an adequate environment for host cell survival and proliferation, fluctuations in NAD(+) or biosynthetic precursors bioavailability have been described during host-pathogen interactions, which will interfere with pathogen persistence or clearance. Here, we review the double-edged sword of NAD(+) metabolism during host-pathogen interactions emphasizing its potential for treatment of infectious diseases.

Keywords: Host-pathogen interaction; L-tryptophan; NAD+/NADH ratio; NADPH; Nicotinamide adenine dinucleotide (NAD+); Sirtuins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bacterial Infections / metabolism
  • Bacterial Physiological Phenomena
  • Biosynthetic Pathways
  • Entamoeba / physiology
  • Entamoebiasis / metabolism
  • Host-Pathogen Interactions*
  • Humans
  • Leishmania / physiology
  • Leishmaniasis / metabolism
  • Malaria / metabolism
  • NAD / metabolism*
  • Plasmodium / physiology
  • Virus Diseases / metabolism
  • Virus Physiological Phenomena

Substances

  • NAD