Kieran Allowitz, Justin Taylor, Kyra Harames, John Yoo, Omar Baloch, Kota V Ramana
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引用次数: 0
摘要
阿尔茨海默氏症、帕金森氏症和肌萎缩侧索硬化症等神经退行性疾病会导致中枢神经系统的神经元受损并逐渐丧失。神经退行性疾病最常见于衰老过程。衰老会导致活性氧增加和线粒体 ATP 生成减少,从而造成氧化还原失衡和氧化应激。氧化应激产生的自由基会对含有多不饱和脂肪酸的膜脂质造成破坏,从而形成有毒的脂醛产物,如 4-羟基壬烯醛和丙二醛。多项研究表明,脂质过氧化产生的醛类产物会与细胞蛋白质形成加合物,改变蛋白质的结构和功能。因此,这些脂质醛可以作为次级信号中间体,改变重要的新陈代谢途径,导致包括神经退行性疾病在内的多种人类疾病的病理生理学。此外,它们还可以作为疾病进展的生物标志物。这篇叙述性综述文章讨论了氧化应激介导的脂质过氧化衍生脂醛在各种神经退行性疾病的病理生理学中的生物学和临床意义。
Oxidative Stress-mediated Lipid Peroxidation-derived Lipid Aldehydes in the Pathophysiology of Neurodegenerative Diseases.
Neurodegenerative diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis cause damage and gradual loss of neurons affecting the central nervous system. Neurodegenerative diseases are most commonly seen in the ageing process. Ageing causes increased reactive oxygen species and decreased mitochondrial ATP generation, resulting in redox imbalance and oxidative stress. Oxidative stress-generated free radicals cause damage to membrane lipids containing polyunsaturated fatty acids, leading to the formation of toxic lipid aldehyde products such as 4- hydroxynonenal and malondialdehyde. Several studies have shown that lipid peroxidation-derived aldehyde products form adducts with cellular proteins, altering their structure and function. Thus, these lipid aldehydes could act as secondary signaling intermediates, modifying important metabolic pathways, and contributing to the pathophysiology of several human diseases, including neurodegenerative disorders. Additionally, they could serve as biomarkers for disease progression. This narrative review article discusses the biological and clinical significance of oxidative stress-mediated lipid peroxidation-derived lipid aldehydes in the pathophysiology of various neurodegenerative diseases.
期刊介绍:
Current Neuropharmacology aims to provide current, comprehensive/mini reviews and guest edited issues of all areas of neuropharmacology and related matters of neuroscience. The reviews cover the fields of molecular, cellular, and systems/behavioural aspects of neuropharmacology and neuroscience.
The journal serves as a comprehensive, multidisciplinary expert forum for neuropharmacologists and neuroscientists.