Parkinson’s Disease (PD) is a neurodegenerative disorder characterized, in part, by the loss of dopaminergic neurons within the nigral-striatal pathway. Multiple lines of evidence support a role for reactive nitrogen species (RNS) in degeneration of this pathway, specifically nitric oxide (NO). This review will focus on how RNS leads to loss of dopaminergic neurons in PD and whether RNS accumulation represents a central signal in the degenerative cascade. Herein, we provide an overview of how RNS accumulates in PD by considering the various cellular sources of RNS including nNOS, iNOS, nitrate, and nitrite reduction and describe evidence that these sources are upregulating RNS in PD. We document that over 1/3 of the proteins that deposit in Lewy Bodies, are post-translationally modified (S-nitrosylated) by RNS and provide a broad description of how this elicits deleterious effects in neurons. In doing so, we identify specific proteins that are modified by RNS in neurons which are implicated in PD pathogenesis, with an emphasis on exacerbation of synucleinopathy. How nitration of alpha-synuclein (aSyn) leads to aSyn misfolding and toxicity in PD models is outlined. Furthermore, we delineate how RNS modulates known PD-related phenotypes including axo-dendritic-, mitochondrial-, and dopamine-dysfunctions. Finally, we discuss successful outcomes of therapeutics that target S-nitrosylation of proteins in Parkinson’s Disease related clinical trials. In conclusion, we argue that targeting RNS may be of therapeutic benefit for people in early clinical stages of PD.

帕金森病 (PD) 是一种神经退行性疾病，其部分特征在于黑质-纹状体通路内多巴胺能神经元的丧失。多条证据支持活性氮（RNS）在该途径退化中的作用，特别是一氧化氮（NO）。本综述将重点关注 RNS 如何导致 PD 中多巴胺能神经元的丧失，以及 RNS 积累是否代表退行性级联中的中心信号。在此，我们通过考虑 RNS 的各种细胞来源（包括 nNOS、iNOS、硝酸盐和亚硝酸盐的还原）来概述 RNS 如何在 PD 中积累，并描述这些来源正在上调 PD 中 RNS 的证据。我们记录了超过 1/3 的蛋白质沉积在路易体中，被 RNS 翻译后修饰（S-亚硝基化），并广泛描述了这如何在神经元中引起有害影响。在此过程中，我们确定了神经元中 RNS 修饰的特定蛋白质，这些蛋白质与 PD 发病机制有关，重点是突触核蛋白病的恶化。概述了 α-突触核蛋白 (aSyn) 的硝化如何导致 PD 模型中的 aSyn 错误折叠和毒性。此外，我们描述了 RNS 如何调节已知的 PD 相关表型，包括轴树突、线粒体和多巴胺功能障碍。最后，我们讨论了在帕金森病相关临床试验中针对蛋白质 S-亚硝基化的治疗的成功结果。总之，我们认为靶向 RNS 可能对处于 PD 早期临床阶段的人具有治疗益处。