Nitric oxide (NO) is a versatile gasotransmitter that contributes in a range of physiological and pathological mechanims depending on its cellular levels. An appropriate concentration of NO is essentially required for cellular physiology; however, its increased level triggers pathological mechanisms like altered cellular redox regulation, functional impairment of mitochondrion, and modifications in cellular proteins and DNA. Its increased levels also exhibit post-translational modifications in protein through S-nitrosylation of their thiol amino acids, which critically affect the cellular physiology. Along with such modifications, NO could also nitrosylate the endoplasmic reticulum (ER)-membrane located sensors of ER stress, which subsequently affect the cellular protein degradation capacity and lead to aggregation of misfolded/unfolded proteins. Since protein aggregation is one of the pathological hallmarks of neurodegenerative disease, NO should be taken into account during development of disease therapies. In this Review, we shed light on the diverse role of NO in both cellular physiology and pathology and discussed its involvement in various pathological events in the context of neurodegenerative diseases.

中文翻译：

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推定的气体递质一氧化氮：罪魁祸首在神经退行性疾病病理学中的作用更新。

一氧化氮（NO）是一种多功能的气体递质，根据其细胞水平而参与多种生理和病理机制。细胞生理学本质上需要适当浓度的NO。然而，其水平升高触发了诸如改变细胞氧化还原调节，线粒体功能受损以及细胞蛋白质和DNA修饰等病理机制。其增加的水平还通过其硫醇氨基酸的S-亚硝基化而在蛋白质中表现出翻译后修饰，这严重影响细胞生理。伴随此类修饰，NO还可以将内质网（ER）膜上的ER应力亚硝化，随后影响细胞蛋白质降解能力并导致错误折叠/未折叠蛋白质的聚集。由于蛋白质聚集是神经退行性疾病的病理特征之一，因此在疾病治疗的发展过程中应考虑NO。在这篇综述中，我们阐明了NO在细胞生理学和病理学中的不同作用，并讨论了其在神经退行性疾病背景下参与各种病理事件的过程。