Clinical perspective on oxidative stress in sporadic amyotrophic lateral sclerosis.
Clinical perspective on oxidative stress in sporadic amyotrophic lateral sclerosis.
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DOI：
10.1016/j.freeradbiomed.2013.06.029
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发表时间：
2013-12
影响因子：
7.4
通讯作者：
Mitsumoto, Hiroshi
中科院分区：
文献类型：
--
作者：
D'Amico, Emanuele;Factor-Litvak, Pam;Santella, Regina M.;Mitsumoto, Hiroshi
关键词：
散发性肌萎缩侧索硬化症（sALS）是最具破坏性的神经系统疾病之一，大多数患者在症状发作后3至4年内死亡。氧化应激是有利于促氧化状态的促氧化/抗氧化平衡的紊乱。ALS的尸检和实验室研究表明，氧化应激在运动神经元变性和星形胶质细胞功能障碍中起主要作用。脑脊液、血浆和尿液中的氧化应激生物标志物升高，表明异常氧化应激在中枢神经系统外产生。我们的综述表明，农业化学品，重金属，兵役，职业运动，过度体力消耗，慢性头部创伤和某些食物可能与ALS风险适度相关，风险与吸烟之间的关联更强。在细胞水平上，这些因素都参与产生氧化应激。实验研究表明，诱导适度氧化应激的损伤的组合可以对运动神经元产生附加的有害影响，这表明在现实世界环境中的多次暴露是重要的。随着疾病的进展，营养缺乏，恶病质，心理压力和即将发生的呼吸衰竭可能会进一步增加氧化应激。此外，越来越多的证据表明ALS可能是一种全身性疾病。实验室，病理学和流行病学证据清楚地支持这一假设，即氧化应激是中央的致病过程中，特别是在遗传易感的个人。如果我们要改善ALS的治疗，精心设计的生化和遗传流行病学研究，结合多学科的研究方法，是必要的，并将提供知识，我们了解ALS的病因，病理生理学和预后至关重要。
Sporadic amyotrophic lateral sclerosis (sALS) is one of the most devastating neurological diseases; most patients die within 3 to 4 years after symptom onset. Oxidative stress is a disturbance in the pro-oxidative/anti-oxidative balance favoring the pro-oxidative state. Autopsy and laboratory studies in ALS indicate that oxidative stress plays a major role in motor neuron degeneration and astrocyte dysfunction. Oxidative stress biomarkers in cerebrospinal fluid, plasma, and urine, are elevated, suggesting that abnormal oxidative stress is generated outside of the central nervous system. Our review indicates that agricultural chemicals, heavy metals, military service, professional sports, excessive physical exertion, chronic head trauma, and certain foods might be modestly associated with ALS risk, with a stronger association between risk and smoking. At the cellular level, these factors are all involved in generating oxidative stress. Experimental studies indicate that a combination of insults that induce modest oxidative stress can exert additive deleterious effects on motor neurons, suggesting multiple exposures in real-world environments are important. As the disease progresses, nutritional deficiency, cachexia, psychological stress, and impending respiratory failure may further increase oxidative stress. Moreover, accumulating evidence suggests that ALS is possibly a systemic disease. Laboratory, pathologic, and epidemiologic evidence clearly support the hypothesis that oxidative stress is central in the pathogenic process, particularly in genetically susceptive individuals. If we are to improve ALS treatment, well-designed biochemical and genetic epidemiological studies, combined with a multidisciplinary research approach, are needed and will provide knowledge crucial to our understanding of ALS etiology, pathophysiology, and prognosis.
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影响因子：
11.2
作者：
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通讯作者：
Thun, MJ
影响因子：
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Oddone, E. Z.
影响因子：
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Newton, RS