Journal
PHARMACOLOGICAL RESEARCH
Volume 135, Issue -, Pages 25-36Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2018.06.022
Keywords
NAMPT; Cytokine; Monocytes; Macrophages
Categories
Funding
- Leonino Fontana and Maria Lionello FIRC fellowship [14832]
- AIRC [IG10509]
- Fondazione Umberto Veronesi
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Nicotinamide phosphoribosyltransferase (NAMPT) is the bottleneck enzyme of the NAD salvage pathway and thereby is a controller of intracellular NAD concentrations. It has been long known that the same enzyme can be secreted by a number of cell types and acts as a cytokine, although its receptor is at present unknown. Investigational compounds have been developed that target the enzymatic activity as well as the extracellular action (Le. neutralizing antibodies). The present contribution reviews the evidence that links intracellular and extracellular NAMPT to myeloid biology, for example governing monocyte/macrophage differentiation, polarization and migration. Furthermore, it reviews the evidence that links this protein to some disorders in which myeloid cells have a prominent role (acute infarct, inflammatory bowel disease, acute lung injury and rheumatoid arthritis) and the data showing that inhibition of the enzymatic activity or the neutralization of the cytokine is beneficial in preclinical animal models.
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