| Project/Area Number |
16H05318
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Tohoku University |
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Principal Investigator |
Aoki Masashi 東北大学, 医学系研究科, 教授 (70302148)
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| Co-Investigator(Kenkyū-buntansha) |
割田 仁 東北大学, 大学病院, 助教 (30400245)
鈴木 直輝 東北大学, 大学病院, 助教 (70451599)
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| Research Collaborator |
OKANO HIDEYUKI
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
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| Keywords | 神経変性 / 多系統蛋白質症 / 封入体ミオパチー / RNA結合蛋白 / iPS細胞 |
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| Outline of Final Research Achievements |
Multisystem proteinopathy (MSP) is an inherited neuromuscular syndrome characterized by progressive and selective degeneration of skeletal muscle, bone, cerebrocortical, and motor neuron with aberrant protein aggregates, resulting in a combination of amyotrophic lateral sclerosis, frontotemporal dementia, inclusion body myopathy (IBM), and Paget disease of bone.
In this study, using patient-derived induced pluripotent stem cells (iPSCs), we have developled motor neurons and skeletal muscle cells with an MSP type 3 (MSP3)-linked hnRNPA1 gene mutation. Isogenic control iPSCs are also under development. To reveal the underlying pathomechanisms particularly related to assembly/disassembly of RNA granules, we are trying to recapitulate pathological phenotypes in these human cellular models of MSP3.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究代表者らは1991年以来、134家系にのぼる家族性の筋萎縮性側索硬化症、および複数の遺伝性筋疾患家系を集積し、その遺伝学的背景を解明する中で本邦初のMSP3家系を見出してきた。本研究により、単なるMSPの病態解明にとどまらず、広く神経細胞－骨格筋細胞が変性する疾患群（封入体ミオパチー、骨Paget病、前頭側頭型認知症、筋萎縮性側索硬化症）に共通するRNA病態にせまることが可能なヒト細胞モデルを確立しつつある。このようなMSP研究は、高齢者人口が増大する中で患者数もまた増加している難治性神経筋疾患の病態解明と治療法開発に寄与することが期待される。
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