Laminarin attenuates neuroinflammation in MPTP-induced Parkinson's disease mouse model via inhibiting dectin-1/Syk/NF-κB signaling.

Neuroinflammation is a critical contributor to the pathogenesis of Parkinson’s disease (PD), characterized by progressive neurodegeneration of dopaminergic neurons and motor impairment. Dectin-1, a C-type lectin pattern recognition receptor (CLR), plays an important role in promoting inflammation. However, the function of Dectin‑1-mediated signaling in PD remains to be elucidated. This study aimed to investigate the neuroprotective effect of laminarin (LAM), a specific antagonist of Dectin-1, on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced mouse model of PD. Our results showed that LAM protected against MPTP-induced motor dysfunction and dopaminergic neuronal apoptosis in a dose-dependent manner in PD mice. MPTP treatment promoted overactivation of microglia and astrocytes in the nigrostriatal pathway, which was reversed by LAM intervention. LAM significantly inhibited MPTP-induced upregulation of Dectin-1 as well as the phosphorylation of Syk and NF-κB in the substantia nigra (SN). Moreover, LAM significantly decreased the mRNA level of iNOS, TNF-α and IL-1β, and suppressed the protein expression of NLRP3, iNOS and COX-2. This study collectively suggests that Dectin-1 plays a pivotal role in MPTP-induced neuroinflammation and neuronal apoptosis. The protective effects of LAM against MPTP-induced neurotoxicity are mediated by inhibition of the Dectin-1/Syk/NF-κB signaling pathway, highlighting the Dectin-1 pathway as a potential therapeutic target for further investigation in PD.