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

Hydrogen sulfide (H2 S) has been regarded as the third gaseous transmitter alongside nitric oxide (NO) and carbon monoxide (CO). In mammalian brain, H2 S is produced redundantly by four enzymatic pathways, implying its abundance in the organ. In physiological conditions, H2 S 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 H2 S with Parkinson's disease. Specifically, the endogenous H2 S level in the substantia nigra (SN) is significantly reduced along with 6-hydroxydopamine (6-OHDA) treatment in rats, while supplementation of H2 S not only reverses 6-OHDA-induced neuronal loss but also attenuates the following disorders of movement, suggesting a protective effect of H2 S 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 H2 S may be a new hope for the treatment of PD. Further studies have shown that the protective effects can be ascribed to H2 S-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 H2 S donors are also conveyed with an emphasis on the treatment of PD. Nevertheless, one should bear in mind that the precise role of H2 S in the pathogenesis of PD remains largely elusive. Therefore, more studies are warranted before turning the hope into a real therapy for PD.