13 reasons why the brain is susceptible to oxidative stress.
13 reasons why the brain is susceptible to oxidative stress.
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DOI：
10.1016/j.redox.2018.01.008
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发表时间：
2018-05
期刊：
影响因子：
11.4
通讯作者：
Bailey DM
中科院分区：
文献类型：
--
作者：
Cobley JN;Fiorello ML;Bailey DM
人类大脑消耗总基础氧（O2）预算的20%来支持ATP密集的神经元活动。如果没有足够的O2来支持ATP需求，神经元活动就会失败，即使是短暂的缺血也会导致神经退行性疾病。虽然O2对大脑功能的重要性是明确的，但氧化应激如何导致神经退行性变尚不明确。之所以存在歧义，是因为大脑易受氧化应激影响的许多原因仍然不清楚。许多被错误地理解为外源O2衍生的自由基和非自由基物质生成的有害结果。为了理解有多少原因支持氧化应激，我们必须首先从积极的角度重新审视自由基和非自由基物质，因为它们的故意产生使大脑能够通过氧化还原信号（即积极功能）实现关键功能（例如突触可塑性）。使用自由基和非自由基衍生物来传递信号，当氧化还原信号传导出错时（即负功能性），会使大脑对氧化应激敏感。为了促进对机制的理解，我们合理化了大脑易受氧化应激影响的13个原因。主要原因包括不饱和脂质富集、线粒体、钙、谷氨酸、适度的抗氧化防御、氧化还原活性过渡金属和神经递质自动氧化。我们回顾RNA氧化作为氧化应激的一个未被充分认识的原因。每种原因之间复杂的相互作用决定了神经元在动态环境中对氧化应激的易感性和神经身份依赖性。我们的论述为研究人员探究健康和疾病中大脑氧化应激的生化基础奠定了基础。大脑故意产生活性物质来传递氧化还原信号。氧化还原信号调节关键功能（例如突触可塑性）。当氧化还原信号出错时，大脑容易受到氧化应激的影响。
The human brain consumes 20% of the total basal oxygen (O2) budget to support ATP intensive neuronal activity. Without sufficient O2 to support ATP demands, neuronal activity fails, such that, even transient ischemia is neurodegenerative. While the essentiality of O2 to brain function is clear, how oxidative stress causes neurodegeneration is ambiguous. Ambiguity exists because many of the reasons why the brain is susceptible to oxidative stress remain obscure. Many are erroneously understood as the deleterious result of adventitious O2 derived free radical and non-radical species generation. To understand how many reasons underpin oxidative stress, one must first re-cast free radical and non-radical species in a positive light because their deliberate generation enables the brain to achieve critical functions (e.g. synaptic plasticity) through redox signalling (i.e. positive functionality). Using free radicals and non-radical derivatives to signal sensitises the brain to oxidative stress when redox signalling goes awry (i.e. negative functionality). To advance mechanistic understanding, we rationalise 13 reasons why the brain is susceptible to oxidative stress. Key reasons include inter alia unsaturated lipid enrichment, mitochondria, calcium, glutamate, modest antioxidant defence, redox active transition metals and neurotransmitter auto-oxidation. We review RNA oxidation as an underappreciated cause of oxidative stress. The complex interplay between each reason dictates neuronal susceptibility to oxidative stress in a dynamic context and neural identity dependent manner. Our discourse sets the stage for investigators to interrogate the biochemical basis of oxidative stress in the brain in health and disease. The brain deliberately produces reactive species to transmit redox signals. Redox signalling regulates critical functions (e.g. synaptic plasticity). The brain is susceptible to oxidative stress when redox signalling goes awry.
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