| Project/Area Number |
23591259
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Hyogo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Keiichiro 兵庫医科大学, 医学部, 教授 (70221322)
SAKIYAMA Haruhiko 兵庫医科大学, 医学部, 講師 (30508958)
EGUCHI Hironobu 兵庫医科大学, 医学部, 講師 (60351798)
YOSHIHARA Daisaku 兵庫医科大学, 医学部, 助教 (00567266)
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| Co-Investigator(Renkei-kenkyūsha) |
URUSHITANI Makoto 京都大学, 医学部, 准教授 (60332326)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
|
| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ALS / SOD1 / 免疫療法 / モノクローナル抗体 / 構造解析 / SOD / NMR |
|---|
| Research Abstract |
Although mutations of Cu,Zn-superoxide dismutase (SOD1) gene is one of causes of Familial Amyotrophic lateral sclerosis (FALS), the mechanism responsible for FALS remains unclear. Because mutant SOD1s are unstable and prone to aggregate, they would have different conformation and reactivity of monoclonal antibodies (mAbs) compared with wild-type SOD1. In this study, we made new various mAbs in order to detect tiny conformational differences between mutant SOD1s and wild-type SOD1. Some mAbs exhibited the different reactivity against the different mutation of SOD1 and labeled Lewy-body-like hyaline inclusions in the spinal cord of ALS model mice by immunohistochemical analysis. Therefore, these mAbs will be useful in detecting the conformational changes of SOD1 by mutation and developing a new ALS immunotherapy. In addition, we determined the crystal structure of SOD1, which will be also useful in determining the structure of SOD1-mAb complex.
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