2014 Fiscal Year Final Research Report
The role of PGE2 receptors in Parkinson's disease
| Project/Area Number |
24590121
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | パーキンソン病 / プロスタグランジンE2 / ＥＰ受容体 / プロスタグランジンE合成酵素 / 炎症 / 神経変性疾患 / 神経細胞死 / ノックアウトマウス |
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| Outline of Final Research Achievements |
Recently, we have found that microsomal PGE synthase (mPGES)-1 plays a crucial role in dopaminergic neurodegeneration in the 6-hydroxydopamine (6-OHDA) model of parkinson’s disease (PD). mPGES-1 was expressed in dopaminergic neurons, but not in microglia and astrocytes, in substantia nigra (SN). We found that mPGES-1 contributes not only to dopaminergic neuronal death through production of PGE2, but also to reduction in dopamine content, impairment of nitro-striatal projection and behavioral disorder assessed by Rotarod test. Furthermore, using in vitro and in vivo PD models, we found that EP3 receptors may have crucial role in mPGES-1 neurotoxicity. Results from excitotoxicity model in SH-SY5Y cells suggest that activation of EP3 receptor deteriorates Glutamate-induced apoptosis by inactivating PKA through Gi activation, followed by activation of caspases with modulation of Bcl-2. Thus EP3 receptor may have the key role in neuronal apoptosis after brain ischemia and also in PD.
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| Free Research Field |
医歯薬学
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