Abstract | 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.
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Authors | Changyoun Kim, Emmanuel Ojo-Amaize, Brian Spencer, Edward Rockenstein, Michael Mante, Paula Desplats, Wolf Wrasidlo, Anthony Adame, Emeka Nchekwube, Olusola Oyemade, Joseph Okogun, Michael Chan, Howard Cottam, Eliezer Masliah |
Journal | Journal of neuroinflammation
(J Neuroinflammation)
Vol. 12
Pg. 236
(Dec 18 2015)
ISSN: 1742-2094 [Electronic] England |
PMID | 26683203
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Diterpenes
- NF-kappa B
- alpha-Synuclein
- hypoestoxide
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Topics |
- Animals
- Disease Models, Animal
- Diterpenes
(pharmacology, therapeutic use)
- Female
- Humans
- Inflammation
(drug therapy, genetics, metabolism)
- Mice
- Mice, Transgenic
- NF-kappa B
(antagonists & inhibitors, metabolism)
- Neocortex
(drug effects, metabolism)
- Parkinson Disease
(drug therapy, genetics, metabolism)
- alpha-Synuclein
(antagonists & inhibitors, biosynthesis)
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