摘要
NAD+ and NADH在能量代谢、线粒体功能和基因表达多种生物进程中起到重要的作用。多项研究表明服用NAD+不仅可以极大地减少氧化性细胞死亡而且可以减少缺血和外伤性脑损伤,意味着NAD+代谢有望成为治疗脑缺血和脑损伤的靶点。收集的证据表明NAD+可以通过多重机制产生其保护作用,包括组织线粒体改变,加强能量代谢,防止实质上地细胞凋亡、坏死和自噬多种形式的细胞死亡,抑制炎症,直接增加细胞和组织的抗氧化能力及激活SIRT1。越来越多的证据显示NADH代谢也可以作为治疗多种神经障碍的潜在治疗靶点。许多研究进一步表明多种NAD+依赖酶如抗衰老酶、聚ADP核糖聚合酶(PARPs)和CD38,可以调节细胞死亡和多种生物进程。本文中,关于NAD+/NADH和NAD+依赖酶在细胞死亡和缺血性脑损伤的作用的近期发现进行了综述。这些发现均表明NAD+/NADH和NAD+依赖酶在氧化应激诱导的细胞死亡和缺血性脑损伤中起到基础性作用,他们也许会成为脑缺血和多种其它神经紊乱的有希望的治疗靶点。
关键词: CD38,细胞死亡,缺血性脑损伤,NAD+,聚ADP核糖聚合酶,抗衰老酶
Current Medicinal Chemistry
Title:NAD+/NADH Metabolism and NAD+-Dependent Enzymes in Cell Death and Ischemic Brain Injury: Current Advances and Therapeutic Implications
Volume: 22 Issue: 10
Author(s): Yingxin Ma, Hui Nie, Heyu Chen, Jiefu Li, Yunyi Hong, Ban Wang, Caixia Wang, Jie Zhang, Wei Cao, Mingchao Zhang, Yongning Xu and Xianting Ding, Shan Kai Yin, Xinkai Qu and Weihai Ying
Affiliation:
关键词: CD38,细胞死亡,缺血性脑损伤,NAD+,聚ADP核糖聚合酶,抗衰老酶
摘要: NAD+ and NADH play crucial roles in a variety of biological processes including energy metabolism, mitochondrial functions, and gene expression. Multiple studies have indicated that NAD+ administration can profoundly decrease oxidative cell death as well as ischemic and traumatic brain injury, suggesting NAD+ metabolism as a promising therapeutic target for cerebral ischemia and head injury. Cumulating evidence has suggested that NAD+ can produce its protective effects by multiple mechanisms, including preventing mitochondrial alterations, enhancing energy metabolism, preventing virtually all forms of cell death including apoptosis, necrosis and autophagy, inhibiting inflammation, directly increasing antioxidation capacity of cells and tissues, and activating SIRT1. Increasing evidence has also suggested that NADH metabolism is a potential therapeutic target for treating several neurological disorders. A number of studies have further indicated that multiple NAD+-dependent enzymes such as sirtuins, polymerase(ADP-ribose) polymerases (PARPs) and CD38 mediate cell death and multiple biological processes. In this article, an overview of the recent findings regarding the roles of NAD+/NADH and NAD+- dependent enzymes in cell death and ischemic brain injury is provided. These findings have collectively indicated that NAD+/NADH and NAD+-dependent enzymes play fundamental roles in oxidative stress-induced cell death and ischemic brain injury, which may become promising therapeutic targets for brain ischemia and multiple other neurological disorders.
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Yingxin Ma, Hui Nie, Heyu Chen, Jiefu Li, Yunyi Hong, Ban Wang, Caixia Wang, Jie Zhang, Wei Cao, Mingchao Zhang, Yongning Xu and Xianting Ding, Shan Kai Yin, Xinkai Qu and Weihai Ying , NAD+/NADH Metabolism and NAD+-Dependent Enzymes in Cell Death and Ischemic Brain Injury: Current Advances and Therapeutic Implications, Current Medicinal Chemistry 2015; 22 (10) . https://dx.doi.org/10.2174/0929867322666150209154420
DOI https://dx.doi.org/10.2174/0929867322666150209154420 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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