2016 Fiscal Year Final Research Report
Novel mechanism of Reelin signaling and its relationship with neuropsychiatric disorders
| Project/Area Number |
26460073
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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 | Nagoya City University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | 脳 / リーリン / 遺伝子改変マウス / プロテアーゼ / 精神神経疾患 |
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| Outline of Final Research Achievements |
The secreted glycoprotein Reelin is believed to play critical roles in the pathogenesis of several neuropsychiatric disorders. The highly basic C-terminal region (CTR) of Reelin is necessary for efficient activation of its downstream signaling. We found that CTR-dependent Reelin functions are required for some specific normal brain functions and that mice lacking the CTR recapitulate some aspects of neuropsychiatric disorders. We also identified ADAMTS-3 as the protease that cleaves and inactivates Reelin in the cerebral cortex and hippocampus. Cleavage by ADAMTS-3 is the major contributor of Reelin inactivation in vivo. Dendritic branching and elongation was increased in ADAMTS-3-deficient mice. Therefore, inhibition of ADAMTS-3 upregulates Reelin activity and may be a potential therapeutic strategy for the prevention or treatment of neuropsychiatric and neurodegenerative disorders.
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| Free Research Field |
分子神経生物学
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