Molecular bases of collagen XXV functions in neurological diseases and healthy aging.
| Project/Area Number |
17K07091
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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 |
Nerve anatomy/Neuropathology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Wakabayashi Tomoko 東京大学, 大学院医学系研究科(医学部), 特任助教 (20530330)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | アルツハイマー病 / コラーゲン / 運動ニューロン / 神経発生 / 脳神経疾患 |
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| Outline of Final Research Achievements |
Collagen XXV has been identified as a component of senile plaques in Alzheimer’s disease. In this study, we demonstrated that collagen XXV affects the compaction of amyloid plaques and consequently the brain dynamics of Aβ.
We also revealed the molecular mechanism of binding of collagen XXV to its interactor RPTPσ/δ, which are implicated in synaptic organization and axon guidance. To elucidate further the pathological mechanism of a congenital cranial dysinnervation disorder (CCDD) caused by mutations in the COL25A1 gene, the effect of mutant collagen XXV on motor innervation was examined. Analysis of muscle-specific Col25a1 KO mice showed that muscle-derived collagen XXV is important for the development of cranial motor neurons. We also showed that CCDD mutations in collagen XXV impair the binding to RPTPσ/δ, resulting in reduced interaction with motor axons.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究ではcollagen XXVがアルツハイマー病や神経発生の障害という複数の疾患に関与するメカニズムについて、分子レベルの研究を行った。Aβの蓄積はアルツハイマー病の最も重要な病因として確立しており、その形成過程に影響をおよぼす因子は、病態解明と疾患修飾療法の創出に重要な役割を果たすと考えられる。一方で、collagen XXVはこどもの脳神経の発達障害の原因とも関わっているが、本研究ではcollagen XXVの変異が脳神経支配に障害を来す分子機序を明らかにした。本研究をモデルとして、各種の運動ニューロン疾患の病態解明にもつながるものと期待される。
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Report
(4 results)
Research Products
(4 results)
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[Journal Article] Roles of collagen XXV and its putative receptors PTP s/d in intramuscular motor innervation and congenital cranial dysinnervation disorder2019
Author(s)
Haruka Munezane, Hiroaki Oizumi, Tomoko Wakabayashi, Shu Nishio, Tomoko Hirasawa, Takashi Sato, Akihiro Harada, Tomoyuki Yoshida, Takahiro Eguchi, Yuji Yamanashi, Tadafumi Hashimoto, Takeshi Iwatsubo
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Journal Title
Cell Reports
Volume: 29
Issue: 13
Pages: 4362-4376
DOI
Related Report
Peer Reviewed / Open Access
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