Department of Pharmacology, Second Military Medical University, Shanghai, China.
Stroke Vasc Neurol. 2019 Apr 5;4(2):83-89. doi: 10.1136/svn-2018-000199. eCollection 2019 Jul.
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.
脑卒中是全球和中国第二大、也是最常见的致死原因,但目前有效的治疗方法却寥寥无几。烟酰胺磷酸核糖转移酶(NAMPT)是哺乳动物烟酰胺腺嘌呤二核苷酸(NAD)补救合成的限速酶,从而影响 NAD 依赖性酶,并构成抵抗各种应激的强大内源性防御系统。越来越多的体外和体内研究表明 NAMPT 对脑卒中具有神经保护作用。在这里,我们从五个潜在的治疗策略综述了 NAMPT 作为脑卒中治疗靶点的直接证据,包括 NAMPT 过表达、重组 NAMPT、NAMPT 激活剂、NAMPT 酶产物烟酰胺单核苷酸(NMN)以及 NMN 前体烟酰胺核苷和烟酰胺,并描述了相关的机制和局限性,为开发针对缺血性和出血性脑卒中的新型有效治疗干预措施提供了有希望的选择。