| Project/Area Number |
22KF0333
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| Project/Area Number (Other) |
21F21410 (2021-2022)
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Multi-year Fund (2023)
Single-year Grants (2021-2022) |
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| Section | 外国 |
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| Review Section |
Basic Section 52020:Neurology-related
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| Research Institution | Keio University |
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Principal Investigator |
ルヴァントゥ ニコラ (2023) 慶應義塾大学, 医学部(信濃町), 特任助教 (90998212)
岡野 栄之 (2021-2022) 慶應義塾大学, 医学部(信濃町), 教授 (60160694)
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| Co-Investigator(Kenkyū-buntansha) |
LEVENTOUX NICOLAS 慶應義塾大学, 医学部(信濃町), 外国人特別研究員
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| Project Period (FY) |
2023-03-08 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2023: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2022: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2021: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | CHCHD2 / astrocytes / iPSC / ALS / PD / Kii ALS/PDC / Astrocytes / MAPT isoforms / Chimeric mouse model |
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| Outline of Research at the Start |
This research investigates whether molecules, typically exosomes from astrocytes, contain proteins or nucleic acids that could contribute to the development of Kii ALS/PDC in neurons, and concerns the engraftment of human progenitors to Rag2-KO pups to improve the chimeric mouse model developed.
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| Outline of Annual Research Achievements |
Previous reports suggest a toxic contribution of astrocytes in ALS and in PD.
We established an original protocol to efficiently generate iPSC-derived astrocytes. We used this protocol to decipher the Kii ALS/PDC, a rare and complex japanese neurological disorder with no genetic or environmental known etiology.
RNA sequencing revealed that Kii-iPasts exhibited abnormal mitochondrial cristae and metabolic alterations. We found CHCHD2, a mitochondria-related gene previously identified as PD-related, significantly downregulated in Kii-iPasts and in neuropathologic specimens of deceased donors. Lentiviral overexpression of CHCHD2 could partially rescue some of these defects, providing a promising therapeutic target for patients.
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