2021 Fiscal Year Final Research Report
Structural abnormality of wild-type Cu/Zn-superoxide dismutase in neurodegenerative disease
| Project/Area Number |
20K22772
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0803:Pathology, infection/immunology, and related fields
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| Research Institution | Keio University |
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Principal Investigator |
Sato Masahiro 慶應義塾大学, 理工学部(矢上), 特任助教 (60877124)
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| Project Period (FY) |
2020-09-11 – 2022-03-31
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| Keywords | SOD1 / ミスフォールディング |
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| Outline of Final Research Achievements |
Mutations to the gene encoding the Cu/Zn-superoxide dismutase (SOD1) protein have been reported as a genetic cause of amyotrophic lateral sclerosis (ALS), and a pathological mechanism has been proposed in which degeneration of spinal motor neurons is accompanied by structural abnormalities (misfolding) of the mutant SOD1 protein. Nonetheless, mutations in the SOD1 gene are not confirmed in most of the ALS cases, and it remains controversial whether SOD1 misfolding is relevant in the pathomechanism of ALS. Therefore, we prepared misfolded SOD1 (misSOD1) in vitro, and by using those misSOD1, we attempted to optimize the experimental conditions to detect misSOD1 in ALS patient samples by immunoprecipitation and ELISA.
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| Free Research Field |
タンパク質科学
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| Academic Significance and Societal Importance of the Research Achievements |
ALSは５０代以降に発症確率が増加する神経変性疾患で、予防法や治療法のない難病であり、その発症メカニズムの解明は急務とされている。ALSの一部には家族歴が見られ、特にSOD1遺伝子に変異が見られることが多く、変異に伴うSOD1タンパク質の構造異常（ミスフォールディング）が毒性を発揮しているという提案がある。よって、構造異常化したSOD1の検出条件を最適化することでALSの早期診断などに展開できるため、意義のある課題である。
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