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

作者：Kim Changyoun; Ojo Amaize Emmanuel; Spencer Brian; Rockenstein Edward; Mante Michael; Desplats Paula; Wrasidlo Wolf; Adame Anthony; Nchekwube Emeka; Oyemade Olusola; Okogun Joseph; Chan Michael; Cottam Howard; Masliah Eliezer^*

来源：Journal of Neuroinflammation, 2015, 12(1): 236.

DOI：10.1186/s12974-015-0455-9

• Hypoestoxide
• Parkinson's disease
• Neuroinflammation
• Neurodegeneration
• alpha-synuclein
• NF-kappa B

Background: Deposition of alpha-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-kappa B 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-alpha-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 alpha-syn transgenic mice. HE administration also prevented the loss of dopaminergic neurons and ameliorated motor behavioral deficits in the alpha-syn transgenic mice, and a-synuclein pathology was significantly reduced by treatment of HE. In addition, increased levels of nuclear phosphorylated NF-kappa B in the frontal cortex of a-syn transgenic mice were significantly reduced by HE administration.
Conclusions: These results support the therapeutic potential of HE for PD and other alpha-synuclein-related diseases.

• 出版日期2015-12-18