Singh Som, William Matthew, Chu Xiang-Ping
Department of Biomedical Sciences, University of Missouri-Kansas City School of Medicine Kansas, Missouri, USA.
Int J Physiol Pathophysiol Pharmacol. 2019 Dec 15;11(6):318-320. eCollection 2019.
Drug addiction is a persistent mental illness and there is no effective treatment. The precise mechanisms underlying addictive responses have not been completely understood, although ion channels, neurotransmitters as well as their receptors, and intracellular endogenous molecules in the brain have been shown to play important roles in cocaine addiction. Nicotinamide phosphoribosyltransferase (NAMPT) is an important rate-limiting enzyme found throughout the body that converts the intracellular pool of nicotinamide adenine dinucleotide (NAD) into nicotinamide mononucleotide (NMN). It reveals a critical role in physiological and pathophysiological conditions such as NAD biosynthesis, aging, inflammation, obesity, diabetes, stroke, motor dysfunction, and cancer. A recent study published in Experimental Neurology by Cen group demonstrated that NAMPT contributes to cocaine reward through sirtuin 1 (SIRT1) signaling in the brain ventral tegmental area. Thus, targeting NAMPT/SIRT1 signaling pathway may provide a promising therapeutic strategy against cocaine addiction.
药物成瘾是一种持续性精神疾病,且尚无有效治疗方法。尽管离子通道、神经递质及其受体以及大脑中的细胞内源性分子已被证明在可卡因成瘾中发挥重要作用,但成瘾反应背后的确切机制尚未完全明确。烟酰胺磷酸核糖转移酶(NAMPT)是一种在全身发现的重要限速酶,它将细胞内的烟酰胺腺嘌呤二核苷酸(NAD)池转化为烟酰胺单核苷酸(NMN)。它在诸如NAD生物合成、衰老、炎症、肥胖、糖尿病、中风、运动功能障碍和癌症等生理和病理生理状况中发挥关键作用。岑研究组最近发表在《实验神经病学》上的一项研究表明,NAMPT通过大脑腹侧被盖区的沉默调节蛋白1(SIRT1)信号通路促进可卡因奖赏效应。因此,靶向NAMPT/SIRT1信号通路可能为对抗可卡因成瘾提供一种有前景的治疗策略。