| Project/Area Number |
25830047
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
WANG Min 東京大学, 教養学部, 特任助教 (10616329)
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| Research Collaborator |
ISHIURA Shoichi
LIU Fang
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | Neurotransmitter / Receptors / Glutamate / Cell Death / Receptor / AMPA |
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| Outline of Final Research Achievements |
The accumulation of glutamate, which occurs immediately after ischemia, results in excessive stimulation of glutamate receptors leading to neurotoxicity. However, clinical application of glutamate receptor antagonists in stroke treatment has failed since these treatments suppress postsynaptic glutamate response that is needed for normal brain function. Therefore, alternative targets/pathways for therapeutic treatment of ischemic stroke must be sought.
We have been able to demonstrate for the first time that the GluR2 AMPAR-mediated neurotoxicity is mediated by a novel mechanism that involve several steps: (1) GAPDH forms a protein complex with AMPAR through its direct interaction with the GluR2NT, (2) AMPAR activation promotes co-internalization and subsequent nuclear translocation of GluR2 and GAPDH, and (3) the formation of the nuclear GAPDH/p53 complex and the activation of nuclear p53-mediated cell death pathways.
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