Nicotinamide Phosphoribosyltransferase as a Target in Inflammation- Related Disorders

Fabrizio      Montecucco; Michele      Cea; Antonia      Cagnetta; Patrizia      Damonte; Aimable      Nahimana; Alberto      Ballestrero; Alberto   Del   Rio; Santina      Bruzzone; Alessio      Nencioni

Abstract

NAD⁺ biosynthesis through nicotinamide phosphoribosyltransferase (NAMPT) holds potential as a target for the treatment of inflammatory disorders due to NAD⁺’s role in immune cell signaling and metabolism. In addition to its activity as an enzyme, NAMPT is also secreted in the extracellular space where it acts as a pro-inflammatory and proangiogenic cytokine. NAMPT inhibition with FK866 has anti-inflammatory activity in different models of immune disorders and it prevents ischemia-reperfusion-induced heart damage by dampening the production of neutrophil chemoattractants. NAMPT blockade with a neutralizing antibody has beneficial effects in an acute lung injury model. Last, but not least, the anticancer activity of NAMPT inhibitors may also reflect, at least in part, their ability to modify the cancer microenvironment through their anti-inflammatory properties. Overall, NAMPT inhibition holds potential for the treatment of inflammation-related disorders and the development of effective and safe NAMPT inhibitors remains an area of strong interest in pharmaceutical research.

Keywords: CD38, chemical inhibitors, inflammation, NAD⁺, NAMPT, PARP, sirtuins.