Jiménez-Jiménez Félix Javier, Alonso-Navarro Hortensia, Herrero María Trinidad, García-Martín Elena, Agúndez José A G
C/ Marroquina 14, 3º B, E-28030 Madrid; Spain.
Curr Med Chem. 2016;23(24):2666-2679. doi: 10.2174/0929867323666160812151356.
The pathogenesis of Parkinson's disease (PD) is not fully understood. Together with some important physiological functions in the Central Nervous System (CNS), nitric oxide (NO) can have both, neuroprotective or neurotoxic actions, depending on its redox state. An important body of evidence suggests the involvement of NO in many of the processes leading to neurodegeneration in several neurological disorders including PD.
The main aim of this review is to update the data regarding the possible involvement of NO in the pathogenesis of PD.
We performed a literature review on neuropathological, biochemical and genetic studies in PD patients and in several experimental models of parkinsonism and role of NO in these models.
Results: Both studies in humans and in experimental models of parkinsonism give support to the contribution of NO in excitotoxicity, inflammation, oxidative stress, mitochondrial function impairment, DNA damage, and Snitrosylation of diverse proteins. The interaction of these mechanisms leads finally to neuronal death. The fact that selective of specific inhibitors of NO synthase (NOS, the enzyme responsible of NO synthesis) should prevent neuronal death through their actions of these pathogenic mechanisms supports the role of NO on PD as well.
NO participates in the pathogenesis of PD by multiple mechanisms described in this review.
帕金森病(PD)的发病机制尚未完全明确。一氧化氮(NO)在中枢神经系统(CNS)中具有一些重要的生理功能,根据其氧化还原状态,它可具有神经保护或神经毒性作用。大量重要证据表明,NO参与了包括PD在内的多种神经系统疾病中导致神经退行性变的许多过程。
本综述的主要目的是更新关于NO可能参与PD发病机制的数据。
我们对PD患者以及帕金森病的几种实验模型的神经病理学、生物化学和遗传学研究以及NO在这些模型中的作用进行了文献综述。
人类研究和帕金森病实验模型研究均支持NO在兴奋性毒性、炎症、氧化应激、线粒体功能损害、DNA损伤以及多种蛋白质的亚硝基化中所起的作用。这些机制的相互作用最终导致神经元死亡。一氧化氮合酶(NOS,负责合成NO的酶)的特异性抑制剂通过作用于这些致病机制可预防神经元死亡,这一事实也支持了NO在PD中的作用。
NO通过本综述中描述的多种机制参与PD的发病过程。