Time to get Personal: A Framework for Personalized Targeting of Oxidative Stress in Neurotoxicity and Neurodegenerative Disease.
Time to get Personal: A Framework for Personalized Targeting of Oxidative Stress in Neurotoxicity and Neurodegenerative Disease.
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DOI：
10.1016/j.cotox.2018.02.003
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发表时间：
2018-03
影响因子：
4.6
通讯作者：
Richardson JR
中科院分区：
文献类型：
--
作者：
Neal M;Richardson JR
2014年，美国神经系统疾病的年度成本为7890亿美元，随着人口老龄化，预计这些数字将在未来50年内显着增加。神经退行性疾病占这些费用的很大一部分。神经退行性疾病的特征在于脑的特定区域中的神经元群体的损失。虽然大多数这些疾病的原因仍然未知，但遗传和环境因素被认为起着重要作用。神经元对变性的独特易感性背后有多种会聚机制，包括衰老、炎症、线粒体功能障碍和氧化应激。氧化应激（OS）是特别重要的，因为有证据表明在神经退行性疾病中损失的神经元群体对OS特别敏感。OS是一种复杂的神经毒性机制，其由自由基（例如活性氧（ROS））的过度产生、抗氧化因子的减少或两者的组合引起。脑的内源性易感性、遗传因素和环境暴露之间的复杂相互作用导致脑中有害的OS生成，并显著促进神经变性的起始和/或进展。不幸的是，神经退行性疾病的治疗方法在临床试验中一直失败。因此，更好地了解遗传易感性和常见的分子机制之间的相互作用的环境贡献者OS的生成可以帮助阐明新的治疗策略，神经退行性疾病。本综述将探讨大脑中氧化应激的现状，因为它与神经毒性有关，特别是探索大脑对OS的内源性易感性、遗传易感性和导致神经毒性的环境暴露背后的常见机制，以确定用于改善治疗结果的精确/个性化医学方法。
The annual cost for neurological disorders in the United States was $789 billion in 2014, and with an aging population these numbers are expected to significantly increase in the next 50 years. Neurodegenerative diseases make up a significant portion of these costs. Neurodegenerative diseases are characterized by the loss of neuronal populations in specific regions of the brain. Although the cause is still unknown for most of these diseases, both genetic and environmental factors are thought to play important roles. There are multiple convergent mechanisms underlying the unique susceptibility of neurons to degeneration, including aging, inflammation, mitochondrial dysfunction, and oxidative stress. Oxidative stress (OS) is of particular importance because evidence indicates that the neuronal populations lost in neurodegenerative diseases are particular susceptible to OS. OS is a complex neurotoxic mechanism that arises from excessive generation of free radicals such as reactive oxygen species (ROS), reduction in anti-oxidant factors, or a combination of the two. A complex interplay between the endogenous susceptibility of the brain, genetic factors, and environmental exposures leads to the harmful generation of OS in the brain and contributes significantly to the initiation and/or progression of neurodegeneration. Unfortunately, therapeutics for neurodegenerative diseases have consistently failed in clinical trials. Thus, a better understanding of the interplay between genetic susceptibility and common molecular mechanisms of environmental contributors to OS generation could aid in elucidation of novel therapeutic strategies for neurodegenerative diseases. This review will explore the current picture of oxidative stress in the brain as it relates to neurotoxicity, specifically exploring common mechanisms behind the endogenous susceptibility of the brain to OS, genetic susceptibility and environmental exposures leading to neurotoxicity, to identify precision/personalized medicine approaches for improving therapeutic outcome.
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DOI：
10.1016/j.bbadis.2013.09.007
发表时间：
2014-08
影响因子：
6.2
作者：
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影响因子：
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DOI：
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发表时间：
2017-06-24
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
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作者：
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通讯作者：
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影响因子：
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