Redox Homeostasis and Cellular Stress Response in Aging and Neurodegeneration
Redox Homeostasis and Cellular Stress Response in Aging and Neurodegeneration
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DOI：
10.1007/978-1-60327-029-8_17
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发表时间：
2010-01-01
期刊：
影响因子：
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通讯作者：
Butterfield, D. Allan
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文献类型：
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作者：
Calabrese, Vittorio;Cornelius, Carolin;Butterfield, D. Allan
抗氧化蛋白的表达和/或活性降低会导致氧化应激、加速衰老和神经退化。虽然压倒性的活性氧(ROS)水平和失控/失调的行为会导致有害的影响，但对这些的更严格的调控在细胞信号转导中都起着重要的作用。导致蛋白质错误折叠的突变以及多不饱和脂肪酸、胆固醇和葡萄糖的自由基氧化产生的有毒产物过载，都会破坏细胞的氧化还原动态平衡。这些效应共同或单独地在细胞中创造了有利于氧化的条件。氧化应激可诱导神经元损伤，调节细胞内信号转导，最终通过细胞凋亡或坏死导致神经元死亡。新的证据表明，同型半胱氨酸(Hcy)，一种天然存在于血浆中的非蛋白质氨基酸，被认为是许多疾病的危险因素。特别是，循环同型半胱氨酸水平的升高已被认为是血管疾病发展的所有独立危险因素(S)。最近的发现强调了升高的同型半胱氨酸水平与神经退化之间的关系，这可以在阿尔茨海默氏症和帕金森氏症中观察到。大脑中存在一种综合反应，以检测和控制各种形式的压力。这是由一个所谓的长寿保证过程的复杂网络完成的，这个过程由几个被称为“维生素”的基因控制。其中，热休克蛋白(HSPs)形成了一个高度保守的系统，负责保存和修复正确的蛋白质构象。最近的研究表明，热休克反应(HSR)有助于在许多人类疾病中发挥细胞保护作用，包括炎症、癌症、衰老和神经退行性疾病。鉴于HSR具有广泛的细胞保护特性，目前研究人员对发现和开发能够诱导HSR的药理制剂越来越感兴趣。L-乙酰肉碱(LAC)被认为是一种治疗多种神经退行性疾病的药物，目前的证据也表明，该化合物可能在健康和疾病条件下的细胞应激反应的调节中发挥关键作用。在这里，我们回顾了新出现的重要概念，强调了神经退化的途径，以及LAC在调节氧化还原依赖的机制中的作用，这些机制导致脑部维生素上调，从而提高大脑的应激耐受性。
Decreased expression and/or activity of antioxidant proteins leads to oxidative stress, accelerated aging, and neurodegeneration. While overwhelming levels and uncontrolled/dysregulated actions of reactive oxygen species (ROS) lead to deleterious effects, tighter regulation of those plays all important role in cell signaling. Mutations causing protein misfolding and the overload of toxic products derived from the free radical oxidation Of polyunsaturated fatty acids, cholesterol, and glucose contribute to the disruption of the cellular redox homeostasis. Collectively or individually, these effects create pro-oxidant conditions in cells. Oxidative stress can induce neuronal damage, modulate intracellular signaling, and call ultimately lead to neuronal death by apoptosis or necrosis. Emerging evidence indicates that homocysteine (Hcy), a non-protein amino acid naturally present in the plasma, is implicated as a risk factor for numerous diseases. In particular, increased levels of circulating Hcy have been recognized as all independent risk factor for the development of vascular disease(s). Recent findings emphasize a relationship between elevated Hcy levels and neurodegeneration, which call be observed in Alzheimer's and Parkinson's diseases. An integrated response exists in the brain to detect and control diverse forms of stress. This is accomplished by a complex network of the so-called longevity assurance processes, which arc controlled by several genes termed "vitagenes." Among these, the heat-shock proteins (HSPs) form a highly conserved system that is responsible for the preservation and repair of the correct protein conformation. Recent studies have shown that the heat-shock response (HSR) contributes to cytoprotection in a number of human diseases including inflammation, cancer, aging, and neurodegenerative disorders. Given the broad cytoprotective properties of the HSR, interest mounts currently among investigators; toward discovering and developing pharmacological agents capable of inducing HSR. L-Acetylcarnitine (LAC) is proposed as a therapeutic agent for several neurodegenerative disorders and also Current evidence suggests that the compound may play a critical role in the modulation of cellular stress response in health and disease conditions. Here, we review the emerging salient concepts highlighting the pathways Of neurodegeneration and the role of LAC in modulating the redox-dependent mechanisms responsible for the upregulation of vitagenes ill brain that leads to the enhancement of stress tolerance in brain.