Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Redox Biol. 2020 Jul;34:101567. doi: 10.1016/j.redox.2020.101567. Epub 2020 May 15.
Nitric oxide (NO) is a multifunctional signalling molecule and a neurotransmitter that plays an important role in physiological and pathophysiological processes. In physiological conditions, NO regulates cell survival, differentiation and proliferation of neurons. It also regulates synaptic activity, plasticity and vesicle trafficking. NO affects cellular signalling through protein S-nitrosylation, the NO-mediated posttranslational modification of cysteine thiols (SNO). SNO can affect protein activity, protein-protein interaction and protein localization. Numerous studies have shown that excessive NO and SNO can lead to nitrosative stress in the nervous system, contributing to neuropathology. In this review, we summarize the role of NO and SNO in the progression of neurodevelopmental, psychiatric and neurodegenerative disorders, with special attention to autism spectrum disorder (ASD). We provide mechanistic insights into the contribution of NO in diverse brain disorders. Finally, we suggest that pharmacological agents that can inhibit or augment the production of NO as well as new approaches to modulate the formation of SNO-proteins can serve as a promising approach for the treatment of diverse brain disorders.
一氧化氮（NO）是一种多功能信号分子和神经递质，在生理和病理生理过程中发挥着重要作用。在生理条件下，NO 调节神经元的存活、分化和增殖。它还调节突触活动、可塑性和囊泡运输。NO 通过蛋白质 S-亚硝基化影响细胞信号转导，即 NO 介导的半胱氨酸硫醇（SNO）的翻译后修饰。SNO 可以影响蛋白质活性、蛋白质-蛋白质相互作用和蛋白质定位。大量研究表明，过多的 NO 和 SNO 会导致神经系统的硝化应激，从而导致神经病理学。在这篇综述中，我们总结了 NO 和 SNO 在神经发育、精神和神经退行性疾病进展中的作用，特别关注自闭症谱系障碍（ASD）。我们提供了关于 NO 在各种脑疾病中作用的机制见解。最后，我们提出，能够抑制或增强 NO 产生的药理学制剂以及调节 SNO-蛋白质形成的新方法，可以作为治疗各种脑疾病的有前途的方法。
