A New Hope for a Devastating Disease: Hydrogen Sulfide in Parkinson's Disease

Hydrogen sulfide (H2S) has been regarded as the third gaseous transmitter alongside nitric oxide (NO) and carbon monoxide (CO). In mammalian brain, H2S is produced redundantly by four enzymatic pathways, implying its abundance in the organ. In physiological conditions, H2S 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 Ca2+ and pH homeostasis in both neuronal cells and glia cells. Intriguingly, emerging evidence indicates a connection of H2S with Parkinson's disease. Specifically, the endogenous H2S level in the substantia nigra (SN) is significantly reduced along with 6-hydroxydopamine (6-OHDA) treatment in rats, while supplementation of H2S not only reverses 6-OHDA-induced neuronal loss but also attenuates the following disorders of movement, suggesting a protective effect of H2S 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 H2S may be a new hope for the treatment of PD. Further studies have shown that the protective effects can be ascribed to H2S-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 H2S donors are also conveyed with an emphasis on the treatment of PD. Nevertheless, one should bear in mind that the precise role of H2S in the pathogenesis of PD remains largely elusive. Therefore, more studies are warranted before turning the hope into a real therapy for PD.