Poster Presenter

Hydrogen Sulfide, A Potential Drug To Treat Parkinson's Disease
Jin-Song Bian, Ming Lu and Li-Fang Hu
Singapore

Parkinson's disease (PD), characterized by a progressive loss of dopaminergic neurons in the substantia nigra (SN), is the second most common neurodegenerative disorder after Alzheimer's disease. We aimed to investigate the role of hydrogen sulfide (H2S), a novel gasotransmitter, in neurodegeneration in rats with 6-hydroxydopamine (6-OHDA) induced Parkinsonism and to examine the underlying mechanisms. Systemic administration with NaHS (an H2S donor) for 3 weeks dose-dependently attenuated the progression of movement dysfunction in rats with unilateral 6-OHDA lesions. Similar results were also found in rotenone-induced PD model. Immunohistochemistry showed that application of NaHS significantly ameliorated the loss of tyrosine-hydroxylase positive (TH+)-neurons in both substantia nigra and striatum. Reduced production of superoxide (O2-) in injured striatum contributed to the protective effect of H2S in this PD model. Moreover, H2S specifically suppressed 6-OHDA evoked NADPH oxidase activation, including translocation of cytosolic subunit p47phox and upregulation of membrane subunit gp91phox. Furthermore, the inhibitory effect of H2S on NADPH oxidase was dependent on suppression of ERK1/2 phosphorylation. In summary, the present study demonstrates for the first time that H2S may serve as a neuroprotectant to treat neurotoxin-induced neurodegeneration via an anti-oxidative mechanism and therefore has potential therapeutic value for treatment of Parkinson's disease.