Galectin-1 attenuates neurodegeneration in Parkinson’s disease model by modulating microglial MAPK/IκB/NFκB axis through its Carbohydrate-recognition domain

Abstract The vicious cycle between the chronic activation of microglia and dopamine neurons degeneration is linked with the progression of Parkinson’s disease (PD). Targeting microglial activation has proven to be a viable option to develop a disease-modified therapy for PD. Galectin-1, which has been reported to have an anti-neuroinflammation effect was used in the present study to evaluate its therapeutic effects on microglia activation and neuronal degeneration in Parkinson’s disease model. It was found that galectin-1 attenuated the inflammatory insult and the apoptosis of SK-N-SH human neuroblastoma cells from conditioned medium of activated microglia induced by Lipopolysaccharides (LPS). Nonetheless, galectin-1 administration (0.5 mg/kg) inhibited the microglia activation, improved the motor deficits in PD mice model induced by MPTP (25 mg/kg weight of mouse, i.p.) and prevented the degeneration of dopaminergic neurons in the substantia nigra. Administration of galectin-1 resulted in p38 and ERK1/2 dephosphorylation followed by IκB/NFκB signaling pathway inhibition. Galectin-1 significantly decreased the secretion of pro-inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). The protective effects and modulation of the MAPK/IκB/NFκB signaling pathway were abolished with β-D-galactose which blocked the carbohydrate-recognition domain of galectin-1. The present study demonstrated that galectin-1 inhibited microglia activation and ameliorated neurodegenerative process in PD model by modulating MAPK/IκB/NFκB axis through its carbohydrate-recognition domain.