Hydrogen sulfide protects dopaminergic neurons via NLRP3 inflammasome inhibition in an MPTP mouse model of Parkinson's disease.

BACKGROUND

Hydrogen sulfide (H2S) has emerged as a potential neuroprotective agent in neurodegenerative diseases, including Parkinson's disease (PD). However, its role in regulating neuroinflammation through the NLRP3 inflammasome remains unclear.

METHODS

We established a PD mouse model using MPTP (30 mg/kg, i.p. for 5 days) and administered NaHS (an H2S donor, 5.6 mg/kg, i.p.) daily during the same period. Behavioral tests, immunohistochemistry, and Western blotting were used to assess motor function, dopaminergic neuron survival, NLRP3 inflammasome activation, and inflammatory cytokine levels.

RESULTS

NaHS significantly improved motor deficits and preserved tyrosine hydroxylase (TH)-positive neurons in the substantia nigra. It markedly suppressed the expression of NLRP3, ASC, cleaved caspase-1, and IL-1β, indicating inhibition of inflammasome activation.

CONCLUSION

Exogenous H2S protects dopaminergic neurons in MPTP-induced PD mice, likely by suppressing NLRP3 inflammasome activation, suggesting its therapeutic potential for PD.