Targeting NAMPT as a therapeutic strategy against stroke

Stroke is the second and the leading most common cause of death in the world and China,respectively,but with few effective therapies.Nicotinamide phosphoribosyltransferase(NAMPT)is the rate-limiting enzyme for nicotinamide adenine dinucleotide(NAD)salvage synthesis in mammals,thereby influencing NAD-dependent enzymes and constituting a strong endogenous defence system against various stresses.Accumulating in-vitro and in-vivo studies have demonstrated the neuroprotective effect of NAMPT in stroke.Here,we review the direct evidence of NAMPT as a promising target against stroke from five potential therapeutic strategies,including NAMPT overexpression,recombinant NAMPT,NAMPT activators,NAMPT enzymatic product nicotinamide mononucleotide(NMN),and NMN precursors nicotinamide riboside and nicotinamide,and describe the relevant mechanisms and limitations,providing a promising choice for developing novel and effective therapeutic interventions against ischaemic and haemorrhagic stroke.