NAMPT as a Therapeutic Target against Stroke. (December 2015)

• Record Type: Journal Article
• Authors: Wang, Pei; Miao, Chao-Yu
• Is Part Of: Trends in pharmacological sciences. Volume 36:Number 12(2015)
• Page Start: 891
• Page End: 905
• Publication Date: 2015-12
• Subjects: Pharmacology -- Periodicals; Pharmacology -- trends -- Periodicals; Pharmacologie -- Périodiques; Pharmacology; Electronic journals; Periodicals; 615.1
• DOI: 10.1016/j.tips.2015.08.012
• Languages: English
• ISSNs: 0165-6147

Abstract

Abstract : Nicotinamide phosphoribosyltransferase (NAMPT), also an adipokine known as visfatin, acts via enzymatic activity to synthesize nicotinamide mononucleotide (NMN) and then to maintain homeostasis of nicotinamide adenine dinucleotide (NAD), which plays a dual role in energy metabolism and biological signaling. Of note, the NAMPT metabolic pathway connects NAD-dependent sirtuin (SIRT) signaling, constituting a strong intrinsic defense system against various stresses. Most recently, studies have demonstrated several mechanisms by which NAMPT might serve as a therapeutic target against ischemic stroke, including cerebroprotection in the acute phase as well as vascular repair and neurogenesis in the chronic phase. The molecular mechanisms underlying these benefits have been explored in vivo and in vitro for neural cells, endothelial progenitor cells, and neural stem cells. Therapeutic interventions using NMN, NAMPT activators, and ischemic conditioning are promising for stroke salvage and rehabilitation. This review discusses the current NAMPT data in the context of translational efforts for stroke treatment. Trends: There is an urgent need for developing new drugs to cure stroke. NAMPT is the rate-limiting enzyme in mammalian NAD biosynthesis. NAMPT–NAD–SIRT cascade constitutes a strong intrinsic defense system against various stresses for cell survival. Accumulating data indicate that NAMPT metabolic signaling exerts multiple forms of protection in stroke processes. Therapeutic interventions by enhancing NAMPT metabolic pathway are promising for stroke salvage and rehabilitation.