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

Abstract

BACKGROUND: Hydrogen sulfide (HS) 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 HS 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 HS protects dopaminergic neurons in MPTP-induced PD mice, likely by suppressing NLRP3 inflammasome activation, suggesting its therapeutic potential for PD.