Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Life Science Institute, National University of Singapore, Singapore, Singapore.
Mol Neurobiol. 2018 May;55(5):3789-3799. doi: 10.1007/s12035-017-0617-0. Epub 2017 May 23.
Hydrogen sulfide (HS) has been regarded as the third gaseous transmitter alongside nitric oxide (NO) and carbon monoxide (CO). In mammalian brain, HS is produced redundantly by four enzymatic pathways, implying its abundance in the organ. In physiological conditions, HS has been found to induce the formation of long-term potential in neuronal cells by augmenting the activity of N-methyl-D-aspartate (NMDA) receptor. Likewise, it also actively takes part in the regulation of intracellular Ca and pH homeostasis in both neuronal cells and glia cells. Intriguingly, emerging evidence indicates a connection of HS with Parkinson's disease. Specifically, the endogenous HS level in the substantia nigra (SN) is significantly reduced along with 6-hydroxydopamine (6-OHDA) treatment in rats, while supplementation of HS not only reverses 6-OHDA-induced neuronal loss but also attenuates the following disorders of movement, suggesting a protective effect of HS in Parkinson's disease (PD). Remarkably, the protective effect has been extensively demonstrated with various in vitro and in vivo PD models. These suggest that HS may be a new hope for the treatment of PD. Further studies have shown that the protective effects can be ascribed to HS-mediated anti-oxidation, anti-inflammation, anti-apoptosis, and pro-survival activity, which are also summarized in the review. Moreover, the progresses on the development of HS donors are also conveyed with an emphasis on the treatment of PD. Nevertheless, one should bear in mind that the precise role of HS in the pathogenesis of PD remains largely elusive. Therefore, more studies are warranted before turning the hope into a real therapy for PD.
硫化氢 (HS) 已被视为继一氧化氮 (NO) 和一氧化碳 (CO) 之后的第三种气体递质。在哺乳动物大脑中，HS 通过四种酶促途径大量产生，这意味着它在器官中含量丰富。在生理条件下，HS 通过增强 N-甲基-D-天冬氨酸 (NMDA) 受体的活性，被发现可以诱导神经元细胞形成长期电位。同样，它还积极参与神经元细胞和神经胶质细胞内 Ca 和 pH 稳态的调节。有趣的是，越来越多的证据表明 HS 与帕金森病有关。具体来说，在大鼠中，随着 6-羟多巴胺 (6-OHDA) 的处理，黑质 (SN) 中的内源性 HS 水平显著降低，而 HS 的补充不仅逆转了 6-OHDA 诱导的神经元丢失，还减轻了随后的运动障碍，表明 HS 在帕金森病 (PD) 中具有保护作用。值得注意的是，这种保护作用已经在各种体外和体内 PD 模型中得到了广泛的证实。这表明 HS 可能是治疗 PD 的新希望。进一步的研究表明，保护作用可以归因于 HS 介导的抗氧化、抗炎、抗凋亡和促生存活性，这也在综述中进行了总结。此外，还传达了 HS 供体开发的进展，重点是 PD 的治疗。然而，人们应该记住，HS 在 PD 发病机制中的确切作用在很大程度上仍不清楚。因此，在将希望转化为 PD 的真正治疗方法之前，还需要进行更多的研究。
