2023 Fiscal Year Annual Research Report
Glia in Neurodegenerative Diseases: a Human Glial Chimeric Mouse Model
| Project/Area Number |
22KF0333
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| Allocation Type | Multi-year Fund |
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| Research Institution | Keio University |
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Principal Investigator |
ルヴァントゥ ニコラ 慶應義塾大学, 医学部(信濃町), 特任助教 (90998212)
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| Project Period (FY) |
2023-03-08 – 2024-03-31
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| Keywords | CHCHD2 / astrocytes / iPSC / ALS / PD |
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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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