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促进细胞烟酰胺腺嘌呤二核苷酸(NAD(+))合成代谢:对衰老及阿尔茨海默病中氧化应激的治疗潜力

Promotion of cellular NAD(+) anabolism: therapeutic potential for oxidative stress in ageing and Alzheimer's disease.

作者信息

Braidy Nady, Guillemin Gilles, Grant Ross

机构信息

University of New South Wales, Faculty of Medicine, Sydney, Australia.

出版信息

Neurotox Res. 2008 May-Jun;13(3-4):173-84. doi: 10.1007/BF03033501.

Abstract

Oxidative imbalance is a prominent feature in Alzheimer's disease and ageing. Increased levels of reactive oxygen species (ROS) can result in disordered cellular metabolism due to lipid peroxdation, protein-cross linking, DNA damage and the depletion of nicotinamide adenine dinucleotide (NAD(+)). NAD(+) is a ubiquitous pyridine nucleotide that plays an essential role in important biological reactions., from ATP production and secondary messenger signaling, to transcriptional regulation and DNA repair. Chronic oxidative stress may be associated with NAD(+) depletion and a subsequent decrease in metabolic regulation and cell viability. Hence, therapies targeted toward maintaining intracellular NAD(+) pools may prove efficacious in the protection of age-dependent cellular damage, in general, and neurodegeneration in chronic central nervous system inflammatory diseases such as Alzheimer's disease, in particular.

摘要

氧化失衡是阿尔茨海默病和衰老的一个显著特征。活性氧(ROS)水平升高可导致细胞代谢紊乱,这是由于脂质过氧化、蛋白质交联、DNA损伤以及烟酰胺腺嘌呤二核苷酸(NAD(+))耗竭所致。NAD(+)是一种普遍存在的吡啶核苷酸,在重要的生物反应中发挥着至关重要的作用,从ATP生成和第二信使信号传导,到转录调控和DNA修复。慢性氧化应激可能与NAD(+)耗竭以及随后代谢调节和细胞活力的下降有关。因此,旨在维持细胞内NAD(+)池的疗法可能总体上对保护年龄依赖性细胞损伤有效,特别是对慢性中枢神经系统炎症性疾病如阿尔茨海默病中的神经退行性变有效。

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