The Role of Nicotinamide Phosphoribosyltransferase in Cerebral Ischemia.
The Role of Nicotinamide Phosphoribosyltransferase in Cerebral Ischemia.
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DOI：
10.2174/1568026615666150610142234
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发表时间：
2015
影响因子：
3.4
通讯作者：
Cao G
中科院分区：
文献类型：
--
作者：
Chen X;Zhao S;Song Y;Shi Y;Leak RK;Cao G
重组组织纤溶酶原激活剂是唯一被批准用于临床治疗急性缺血性脑卒中的药物。因此，对新型中风治疗的迫切需求尚未得到满足。对抗中风的内源性防御机制可能是中风新疗法的关键。大量研究表明烟酰胺磷酸核糖基转移酶（NAMPT）是改善中风后恢复的有吸引力的候选者。作为一种多功能蛋白，NAMPT 在免疫、代谢、衰老、炎症和应激反应中发挥着重要作用。 NAMPT 存在于细胞内和细胞外空间。作为一种限速酶，细胞内形式 (iNAMPT) 催化从烟酰胺生物合成烟酰胺腺嘌呤二核苷酸 (NAD) 的第一步。 iNAMPT 密切调节能量代谢，增强内皮细胞增殖，抑制细胞凋亡，调节血管张力，并在中风等疾病中刺激自噬。细胞外 NAMPT (eNAMPT) 也称为内脏脂肪素（内脏脂肪来源的脂肪因子），具有多效性。人们普遍认为，eNAMPT 的多种生物学功能归因于其 NAMPT 酶活性。然而，eNAMPT对缺血性损伤的影响仍存在争议。一些作者认为，eNAMPT 通过触发神经胶质细胞释放 TNF-α，以非酶促方式加剧缺血性神经元损伤。此外，NAMPT还参与高血压、动脉粥样硬化、缺血性心脏病等多种病理生理过程。因此，目前尚不清楚 NAMPT 在什么条件下是有益的或具有破坏性的。最近使用体外和体内遗传/药理学操作的工作，包括我们自己的研究，提高了我们对 NAMPT 的理解。本综述重点关注 NAMPT 在正常和缺血条件下的多方面和复杂作用。
Recombinant tissue plasminogen activator is the only drug approved for the clinical treatment of acute ischemic stroke. Thus, there is an urgent unmet need for novel stroke treatments. Endogenous defense mechanisms against stroke may hold the key to new therapies for stroke. A large number of studies suggest that nicotinamidephosphoribosyl-transferase (NAMPT) is an attractive candidate to improve post-stroke recovery. As a multifunctional protein, NAMPT plays important roles in immunity, metabolism, aging, inflammation, and stress responses. NAMPT exists in both the intracellular and extracellular space. As a rate-limiting enzyme, intracellular form (iNAMPT) catalyzes the first step in the biosynthesis of nicotinamide adenine dinucleotide (NAD) from nicotinamide. iNAMPT closely regulates energy metabolism, enhancing the proliferation of endothelial cells, inhibiting apoptosis, regulating vascular tone, and stimulating autophagy in disease conditions such as stroke. Extracellular NAMPT (eNAMPT) is also known as visfatin (visceral fat–derived adipokine) and has pleotropic effects. It is widely believed that the diverse biological functions of eNAMPT are attributed to its NAMPT enzymatic activity. However, the effects of eNAMPT on ischemic injury are still controversial. Some authors have argued that eNAMPT exacerbates ischemic neuronal injury non-enzymatically by triggering the release of TNF-α from glial cells. In addition, NAMPT also participates in several pathophysiological processes such as hypertension, atherosclerosis, and ischemic heart disease. Thus, it remains unclear under what conditions NAMPT is beneficial or destructive. Recent work using in vitro and in vivo genetic/pharmacologic manipulations, including our own studies, has improved our understanding of NAMPT. This review focuses on the multifaceted and complex roles of NAMPT under normal and ischemic conditions.
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