Parkinson’s disease (PD) is a neurodegenerative disordercharacterized by a progressive loss of dopaminergic neu-rons in the substantia nigra (SN). The present study wasdesigned to examine the therapeutic effect of hydrogensulfide (H2S, a novel biological gas) on PD. The endoge-nous H2S level was markedly reduced in the SN in a6-hydroxydopamine (6-OHDA)-induced PD rat model. Sys-temic administration of NaHS (an H2S donor) dramatically reversed the progression of movement dysfunction, loss of tyrosine-hydroxylase positive neurons in the SN and the elevated malondialdehyde level in injured striatum in the 6-OHDA-induced PD model. H2S specifically inhibited6-OHDA evoked NADPH oxidase activation and oxygenconsumption. Similarly, administration of NaHS also pre-vented the development of PD induced by rotenone. NaHS treatment inhibited microglial activation in the SNand accumulation of pro-inflammatory factors (e.g. TNF-aand nitric oxide) in the striatum via NF-jB pathway. More-over, significantly less neurotoxicity was found in neu-rons treated with the conditioned medium from microgliaincubated with both NaHS and rotenone compared tothat with rotenone only, suggesting that the therapeutic effect of NaHS was, at least partially, secondary to its sup-pression of microglial activation. In summary, we demon-strate for the first time that H2S may serve as a neuroprotectant to treat and prevent neurotoxin-inducedneurodegeneration via multiple mechanisms includinganti-oxidative stress, anti-inflammation and metabolicinhibition and therefore has potential therapeutic value for treatment of PD.
Key words: hydrogen sulfide; metabolic inhibition; neuroinflammation; neuroprotection; oxidative stress;Parkinson’s disease. CLICK TO REVIEW