Elucidation of ALS pathophysiology using monoclonal antibodies that specifically recognizes SOD1 aggregates
| Project/Area Number |
16K13060
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Applied health science
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| Research Institution | Hyogo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
吉原 大作 兵庫医科大学, 医学部, 助教 (00567266)
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| Research Collaborator |
WAGATSUMA michiru
EGUCHI hironobu
SAKIYAMA haruhiko
SUZUKI keiichiro
FURUKAWA yoshiaki
TOKUDA eiichi
TACHIBANA taro
KATO shinsuke
URUSHITANI makoto
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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 |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | SOD1 / ALS / タンパク質凝集 / QCM / アミロイド / 筋萎縮性側索硬化症 / モノクロ－ナル抗体 / 凝集 / Cu,Zn-スーパーオキシドディスムターゼ / 免疫組織染色 / エピトープ |
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| Outline of Final Research Achievements |
Although Cu,Zn-superoxide dismutase (SOD1) is one of causes of Amyotrophic lateral sclerosis (ALS), the mechanism responsible for ALS remains unclear. SOD1 is prone to make aggregates or amyloid like fibrils under some conditions. Monoclonal antibodies (mAbs) that recognize misfolded SOD1would help understand ALS pathophysiology and develop a new ALS immunotherapy. In this study, we made new various mAbs having different reactivities for SOD1 fibrils and detecting inclusions in the spinal cord of ALS model mice. In addition, we found that SOD1 undergoes hydrogelation with the formation of amyloid-like fibrils and that these conversions are pH-dependent. Monitoring by a quartz crystal microbalance with admittance analysis (QCM-A) showed that water-rich state before intermolecular assembling is required for fibrillation and hydrogelation in the case of SOD1.
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| Academic Significance and Societal Importance of the Research Achievements |
筋萎縮性側索硬化症（ALS)は運動神経細胞が特異的に障害される難病である。Cu,Zn-スーパーオキシドディスムターゼ（SOD1）の変異が家族性ALSを引き起こすことが明らかになっているが、未だ発症機構の解明がなされておらず、有効な治療法も見つかっていない。孤発性ALSでも野生型SOD1タンパク質の凝集や線維化がALS病態に関与していることが報告されつつある。今回開発したモノクローナル抗体はALS病変部位を特異的に免疫組織染色することができた。また線維化SOD1に反応しやすい抗体も見つかった。これらの抗体はALS診断マーカーや抗体医薬の開発にもつながると期待できる。
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Report
(4 results)
Research Products
(14 results)
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[Presentation] Cu/Zn-Superoxide Dismutase Forms hydrogels composed of amyloid fibrils in a pH-Dependent Manner2018
Author(s)
Noriko Fujiwara, Michiru Wagatsuma, Naoto Oba, Daisaku Yoshihara, Eiichi Tokuda, Haruhiko Sakiyama, Hironobu Eguchi, Motoko Ichihashi, Yoshiaki Furukawa, Tadashi Inoue, Keiichiro Suzuki
Organizer
APPS2018
Related Report
Int'l Joint Research
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