NAD+ Metabolism and NAD+-Dependent Enzymes: Promising Therapeutic Targets for Neurological Diseases
NAD+ Metabolism and NAD+-Dependent Enzymes: Promising Therapeutic Targets for Neurological Diseases
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NAD 代谢和 NAD 依赖性酶：神经系统疾病的有希望的治疗靶点
DOI：
10.2174/138945012799201711
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发表时间：
2012-02-01
影响因子：
3.2
通讯作者：
Ying, Weihai
中科院分区：
文献类型：
--
作者：
Ma, Yingxin;Chen, Heyu;Ying, Weihai
大量研究表明，氧化应激、线粒体改变、钙稳态异常和炎症等四种相互作用的因素在脑卒中、阿尔茨海默病（AD）和帕金森病（PD）等多种主要神经系统疾病中起着至关重要的病理作用。越来越多的证据表明，NAD（+）不仅在线粒体功能和能量代谢中起重要作用，而且在钙稳态和炎症中也起重要作用。NAD（+）消耗的关键酶---聚（ADP-核糖）聚合酶-1（PARP-1）和sirtuins也被证明在细胞死亡和衰老中起重要作用，这是多种主要年龄依赖性神经疾病病理学中的两个关键因素：PARP-1在炎症和氧化应激诱导的细胞死亡中起关键作用;而sirtuins也介导衰老、细胞死亡和炎症的过程。因此，可以想象，越来越多的证据表明NAD（+）代谢和NAD（+）依赖性酶是治疗许多神经系统疾病的有希望的靶点。例如，NAD（+）依赖性的关键酶SIRT 1和SIRT 2已被证明强烈影响PD和AD的病理变化; PARP-1抑制剂可显著减轻多种神经系统疾病动物模型的脑损伤; NAD（+）或烟酰胺给药也可减轻缺血性脑损伤。未来的研究有必要进一步研究NAD（+）代谢和NAD（+）依赖性酶在神经系统疾病中的作用，这可能会揭示治疗衰弱性疾病的新靶点。
Numerous studies have indicated that four interacting factors, including oxidative stress, mitochondrial alterations, calcium dyshomeostasis and inflammation, play crucial pathological roles in multiple major neurological diseases, including stroke, Alzheimer's disease (AD) and Parkinson's disease (PD). Increasing evidence has also indicated that NAD(+) plays important roles in not only mitochondrial functions and energy metabolism, but also calcium homeostasis and inflammation. The key NAD(+)-consuming enzyme --- poly (ADP-ribose) polymerase-1 (PARP-1) and sirtuins --- have also been shown to play important roles in cell death and aging, which are two key factors in the pathology of multiple major age-dependent neurological diseases: PARP-1 plays critical roles in both inflammation and oxidative stress-induced cell death; and sirtuins also mediate the process of aging, cell death and inflammation. Thus, it is conceivable that increasing evidence has suggested that NAD(+) metabolism and NAD(+)-dependent enzymes are promising targets for treating a number of neurological illnesses. For examples, the key NAD(+)-dependent enzymes SIRT1 and SIRT2 have been indicated to strongly affect the pathological changes of PD and AD; PARP-1 inhibition can profoundly reduce the brain injury in the animal models of multiple neurological diseases; and administration of either NAD(+) or nicotinamide can also decrease ischemic brain damage. Future studies are necessary to further investigate the roles of NAD(+) metabolism and NAD(+)-dependent enzymes in neurological diseases, which may expose novel targets for treating the debilitating illnesses.