The development of oxidative stress, in which production of highly reactive oxygen species (ROS) overwhelms antioxidant defenses, is a feature of many neurological diseases: ischemic, inflammatory, metabolic and degenerative. Oxidative stress is increasingly implicated in a number of neurodegenerative disorders characterized by abnormal filament accumulation or deposition of abnormal forms of specific proteins in affected neurons, like Alzheimer's disease (AD), Pick's disease, Lewy bodies related diseases, amyotrophic lateral sclerosis (ALS), and Huntington disease. Causes of neuronal death in neurodegenerative diseases are multifactorial. In some familiar cases of ALS mutation in the gene for Cu/Zn superoxide dismutase (SOD1) can be identified. In other neurodegenerative diseases ROS have some, usually not clear, role in early pathogenesis or implications on neuronal death in advanced stages of illness. The effects of oxidative stress on "post-mitotic cells", such as neurons may be cumulative, hence, it is often unclear whether oxidative damage is a cause or consequence of neurodegeneration. Peroxidation of cellular membrane lipids, or circulating lipoprotein molecules generates highly reactive aldehydes among which one of most important is 4-hydroxynonenal (HNE). The presence of HNE is increased in brain tissue and cerebrospinal fluid of AD patients, and in spinal cord of ALS patients. Immunohistochemical studies show presence of HNE in neurofibrilary tangles and in senile plaques in AD, in the cytoplasm of the residual motor neurons in sporadic ALS, in Lewy bodies in neocortical and brain stem neurons in Parkinson's disease (PD) and in diffuse Lewy bodies disease (DLBD). Thus, increased levels of HNE in neurodegenerative disorders and immunohistochemical distribution of HNE in brain tissue indicate pathophysiological role of oxidative stress in these diseases, and especially HNE in formation of abnormal filament deposites.

中文翻译：

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4-羟壬醛和神经退行性疾病。

氧化应激的发展是许多神经系统疾病（缺血性，炎性，代谢性和变性性疾病）的特征，其中高反应性氧类（ROS）的产生使抗氧化防御能力不堪重负。氧化应激越来越多地涉及到许多神经退行性疾病，这些疾病的特征是受影响的神经元中的丝异常聚集或特定蛋白质的异常形式沉积，例如阿尔茨海默氏病（AD），匹克氏病，路易体相关疾病，肌萎缩性侧索硬化症（ALS），和亨廷顿病。神经退行性疾病中神经元死亡的原因是多方面的。在某些熟悉的情况下，可以鉴定出Cu / Zn超氧化物歧化酶（SOD1）基因中的ALS突变。在其他神经退行性疾病中，ROS有一些（通常不清楚）在早期发病机制中的作用或对疾病晚期神经元死亡的影响。氧化应激对诸如神经元之类的“有丝分裂后细胞”的影响可能是累积性的，因此，通常不清楚氧化损伤是神经变性的原因还是后果。细胞膜脂质的过氧化或循环的脂蛋白分子产生高反应性醛，其中最重要的醛是4-羟基壬烯醛（HNE）。AD患者的脑组织和脑脊液中以及ALS患者的脊髓中HNE的存在增加。免疫组织化学研究显示，HNE在AD的神经原纤维缠结和老年斑，散发性ALS残余运动神经元的细胞质，新皮层的路易体和帕金森氏症的脑干神经元中存在 氏病（PD）和弥漫性路易体病（DLBD）。因此，神经退行性疾病中HNE水平的升高和脑组织中HNE的免疫组织化学分布表明这些疾病中氧化应激的病理生理作用，尤其是HNE在异常丝沉积中的形成。