Oxidative stress and neuroinflammation in Alzheimer's disease and amyotrophic lateral sclerosis: common links and potential therapeutic targets.
Oxidative stress and neuroinflammation in Alzheimer's disease and amyotrophic lateral sclerosis: common links and potential therapeutic targets.
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DOI：
10.3233/jad-2004-6206
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
M. Mhatre;R. Floyd;K. Hensley
中科院分区：
文献类型：
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作者：
M. Mhatre;R. Floyd;K. Hensley
许多神经系统疾病，包括阿尔茨海默病（AD）和肌萎缩侧索硬化症（ALS），现在被认为是共享非典型炎症反应作为一个主要的病理特征。神经炎症既可以是慢性氧化应激的原因，也可以是慢性氧化应激的结果。细胞因子刺激的小胶质细胞产生大量的活性氧和活性氮，对周围神经元产生压力。相反，氧化剂可以刺激神经胶质细胞中促炎基因的转录，导致各种炎症反应。这篇综述比较了AD和ALS中神经炎症的文献，特别强调了肿瘤坏死因子α（TNF α）和异常花生四烯酸代谢在慢性氧化条件的发生中所起的作用。基于我们在ALS的G93 A-SOD 1小鼠模型中的观察，以及阿尔茨海默病的发现，我们假设TNFa信号传导轴和神经炎症在这两种疾病的发病机制中具有突出的病理作用。讨论了神经炎症的相关性，以潜在的治疗意义为ALS和AD。
Many neurological diseases, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), are now recognized to share atypical inflammatory reactions as a major pathological feature. Neuroinflammation can both be a cause, and a consequence, of chronic oxidative stress. Cytokine-stimulated microglia generate copious amounts of reactive oxygen and reactive nitrogen species, creating a stress upon ambient neurons. Conversely, oxidants can stimulate pro-inflammatory gene transcription in glia, leading to various inflammatory reactions. This review compares literature regarding neuroinflammation in AD and ALS, with special emphasis on roles played by tumor necrosis factor alpha (TNFalpha) and aberrant arachidonic acid metabolism in the genesis of chronic oxidative conditions. Based on our observations made in the G93A-SOD1 mouse model of ALS, and a body of Alzheimer's disease findings, we hypothesize a prominent pathological role for the TNFalpha-signaling axis and neuroinflammation in the pathogenesis of both diseases. A discussion is made regarding the relevance of neuroinflammation to potential therapeutic implications for both ALS and AD.