Title:Nicotinamide Phosphoribosyltransferase as a Target in Inflammation- Related Disorders
Volume: 13
Issue: 23
Author(s): Fabrizio Montecucco, Michele Cea, Antonia Cagnetta, Patrizia Damonte, Aimable Nahimana, Alberto Ballestrero, Alberto Del Rio, Santina Bruzzone and Alessio Nencioni
Affiliation:
Keywords:
CD38, chemical inhibitors, inflammation, NAD+, NAMPT, PARP, sirtuins.
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.