Abstract / Summary
Cysteinyl leukotriene receptor 1 (CysLTR1) has been implicated in various inflammatory conditions; however, its role in Parkinson’s disease (PD) pathogenesis remains to be explored. This study elucidated the neuroprotective potential of montelukast pre-treatment in rotenone-exposed SH-SY5Y cells in vitro. Notably, montelukast effectively attenuated rotenone-induced upregulation of CysLTR1, suppressed the p38-MAPKAPK2 signalling axis, and reduced pro-inflammatory cytokines. mitigated oxidative stress cascades and restored antioxidant enzyme levels, including activation of the NRF2-KEAP1 axis. Furthermore, montelukast treatment restored dynamin-related protein 1 (DRP1) levels, preserved tyrosine hydroxylase (TH) and PARK7/DJ1 expression, and reduced α-synuclein accumulation in SH-SY5Y cells. Montelukast showed neuroprotective effects by alleviating oxidative stress, modulating the inflammatory response, and preserving key PD biomarkers against rotenone-induced cellular damage. The outcomes imply the potential for repurposing montelukast as a therapeutic option for PD. Clinical trial number: Not applicable.