Hypoestoxide reduces neuroinflammation and aα-synuclein accumulation in a mouse model of Parkinson's disease

Abstract

Background: Deposition of aα-synuclein and neuroinflammation are key pathological features of Parkinson's disease (PD). There is no cure for the disease; however, targeting the pathological features might be available to modulate the disease onset and progression. Hypoestoxide (HE) has been demonstrated as a NF-ΚB modulator, thereby acting as a potential anti-inflammatory and anti-cancer drug. Methods: In order to assess the effect of HE in a mouse model of PD, mThy1-aα-syn transgenic mice received intraperitoneal (IP) injections of either vehicle or HE (5 mg/kg) daily for 4 weeks. Results: Treatment of HE decreased microgliosis, astrogliosis, and pro-inflammatory cytokine gene expression in aα-syn transgenic mice. HE administration also prevented the loss of dopaminergic neurons and ameliorated motor behavioral deficits in the aα-syn transgenic mice, and aα-synuclein pathology was significantly reduced by treatment of HE. In addition, increased levels of nuclear phosphorylated NF-ΚB in the frontal cortex of aα-syn transgenic mice were significantly reduced by HE administration. Conclusions: These results support the therapeutic potential of HE for PD and other aα-synuclein-related diseases.