NADPH oxidase in brain injury and neurodegenerative disorders.
NADPH oxidase in brain injury and neurodegenerative disorders.
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DOI：
10.1186/s13024-017-0150-7
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发表时间：
2017-01-17
影响因子：
15.1
通讯作者：
Brann DW
中科院分区：
文献类型：
--
作者：
Ma MW;Wang J;Zhang Q;Wang R;Dhandapani KM;Vadlamudi RK;Brann DW
氧化应激是阿尔茨海默病、帕金森病、亨廷顿病、肌萎缩侧索硬化症和多发性硬化症等神经退行性疾病以及缺血性和创伤性脑损伤的病理学的共同点。由于其高代谢需求，大脑非常容易受到氧化损伤。然而，试图清除自由基的疗法收效甚微。通过将重点转移到抑制破坏性自由基的产生，最近的研究已确定 NADPH 氧化酶是疾病病理学的主要贡献者。 NADPH氧化酶的主要功能是产生自由基。特别是，越来越多的证据表明，多种神经退行性因子可以上调亚型 NOX1、NOX2 和 NOX4。最近的大多数研究表明，NADPH 氧化酶的遗传和药理学抑制具有神经保护作用，能够减少缺血性和创伤性脑损伤以及慢性神经退行性疾病后病理学的有害方面。本综述旨在总结支持 NADPH 氧化酶在这些神经系统疾病病理学中作用的证据，探索针对这一主要氧化应激途径的药理学策略，并概述将这些疗法成功转化为临床需要克服的障碍。
Oxidative stress is a common denominator in the pathology of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and multiple sclerosis, as well as in ischemic and traumatic brain injury. The brain is highly vulnerable to oxidative damage due to its high metabolic demand. However, therapies attempting to scavenge free radicals have shown little success. By shifting the focus to inhibit the generation of damaging free radicals, recent studies have identified NADPH oxidase as a major contributor to disease pathology. NADPH oxidase has the primary function to generate free radicals. In particular, there is growing evidence that the isoforms NOX1, NOX2, and NOX4 can be upregulated by a variety of neurodegenerative factors. The majority of recent studies have shown that genetic and pharmacological inhibition of NADPH oxidase enzymes are neuroprotective and able to reduce detrimental aspects of pathology following ischemic and traumatic brain injury, as well as in chronic neurodegenerative disorders. This review aims to summarize evidence supporting the role of NADPH oxidase in the pathology of these neurological disorders, explores pharmacological strategies of targeting this major oxidative stress pathway, and outlines obstacles that need to be overcome for successful translation of these therapies to the clinic.