Nicotinamide phosphoribosyltransferase contributes to cocaine addiction through sirtuin 1.

International journal of physiology, pathophysiology and pharmacology Pub Date : 2019-12-15 eCollection Date: 2019-01-01
Som Singh, Matthew William, Xiang-Ping Chu
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Abstract

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.

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烟酰胺磷酸核糖基转移酶通过sirtuin 1参与可卡因成瘾。
药物成瘾是一种持续性的精神疾病,没有有效的治疗方法。尽管离子通道、神经递质及其受体和大脑细胞内内源性分子已被证明在可卡因成瘾中起重要作用,但成瘾反应的确切机制尚不完全清楚。烟酰胺磷酸核糖基转移酶(NAMPT)是一种重要的限速酶,可将细胞内的烟酰胺腺嘌呤二核苷酸(NAD)转化为烟酰胺单核苷酸(NMN)。它揭示了生理和病理生理条件的关键作用,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。Cen小组最近发表在《实验神经病学》上的一项研究表明,NAMPT通过大脑腹侧被盖区SIRT1信号传导促进可卡因奖励。因此,靶向NAMPT/SIRT1信号通路可能为可卡因成瘾提供一种有希望的治疗策略。
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