The prevalence of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), is currently a major public health concern due to the lack of efficient disease-modifying therapeutic options. Recent evidence suggests that mitochondrial dysfunction and nitrosative/oxidative stress are key common mediators of pathogenesis. In this review, we highlight molecular mechanisms linking NO-dependent post-translational modifications, such as cysteine S-nitrosylation and tyrosine nitration, to abnormal mitochondrial metabolism. We further discuss the hypothesis that pathological levels of NO compromise brain energy metabolism via aberrant S-nitrosylation of key enzymes in the tricarboxylic acid (TCA) cycle and oxidative phosphorylation, contributing to neurodegenerative conditions. A better understanding of these pathophysiological events may provide a potential pathway for designing novel therapeutics to ameliorate neurodegenerative disorders.

中文翻译：

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“SNO”-风暴损害神经退行性疾病中的蛋白质活性和线粒体代谢

由于缺乏有效的疾病修饰治疗选择，包括阿尔茨海默病 (AD) 和帕金森病 (PD) 在内的神经退行性疾病的流行是目前一个主要的公共卫生问题。最近的证据表明，线粒体功能障碍和亚硝化/氧化应激是发病机制的关键常见介质。在这篇综述中，我们重点介绍了将 NO 依赖性翻译后修饰（如半胱氨酸 S-亚硝基化和酪氨酸硝化）与异常线粒体代谢联系起来的分子机制。我们进一步讨论了以下假设：NO 的病理水平通过三羧酸 (TCA) 循环中关键酶的异常 S-亚硝基化和氧化磷酸化来损害脑能量代谢，从而导致神经退行性疾病。