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.
Current Topics in Medicinal Chemistry
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.
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Montecucco Fabrizio, Cea Michele, Cagnetta Antonia, Damonte Patrizia, Nahimana Aimable, Ballestrero Alberto, Rio Del Alberto, Bruzzone Santina and Nencioni Alessio, Nicotinamide Phosphoribosyltransferase as a Target in Inflammation- Related Disorders, Current Topics in Medicinal Chemistry 2013; 13 (23) . https://dx.doi.org/10.2174/15680266113136660208
DOI https://dx.doi.org/10.2174/15680266113136660208 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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