RAGE Silencing Ameliorates Neuroinflammation by Inhibition of p38-NF-κB Signaling Pathway in Mouse Model of Parkinson's Disease

Accumulating evidence suggested that neuroinflammation played a crucial role in dopaminergic neuronal death in Parkinson's disease (PD). The receptor for advanced glycation end products (RAGE), a multi-ligand receptor of the immunoglobulin superfamily, has been proposed as a key molecule in the onset and sustainment of the inflammatory response. Engagement of RAGE contributed to neuroinflammation by upregulating nuclear factor-kappa B (NF-kappa B) as well as cytokines. The aim of the present study was to investigate the expression of RAGE in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice and elucidate the RAGE signal pathway involved in the inflammation. Results showed that RAGE protein and pro-inflammatory cytokines cyclooxygenase type 2 (COX-2) were upregulated in MPTP-treated mice. Further experiments showed that RAGE ablation inhibited phosphorylation of I kappa B and p38 and protected nigral dopaminergic neurons against cell death in the substantia nigra (SN). These results suggested that RAGE participated in the pathogenesis of PD by neuroinflammation and p38MAPK-NF kappa B signal pathway may be involved in the process. Moreover, interfering with RAGE signaling pathway may be a reasonable therapeutic option in slowing PD development and progression.