1区 · 医学
ArticleOA
作者: Cottam, Howard ; Spencer, Brian ; Nchekwube, Emeka ; Ojo-Amaize, Emmanuel ; Masliah, Eliezer ; Adame, Anthony ; Desplats, Paula ; Oyemade, Olusola ; Rockenstein, Edward ; Chan, Michael ; Mante, Michael ; Wrasidlo, Wolf ; Okogun, Joseph ; Kim, Changyoun
BACKGROUND:Deposition of α-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-α-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 α-syn transgenic mice. HE administration also prevented the loss of dopaminergic neurons and ameliorated motor behavioral deficits in the α-syn transgenic mice, and α-synuclein pathology was significantly reduced by treatment of HE. In addition, increased levels of nuclear phosphorylated NF-κB in the frontal cortex of α-syn transgenic mice were significantly reduced by HE administration.
CONCLUSIONS:These results support the therapeutic potential of HE for PD and other α-synuclein-related diseases.