2013 Fiscal Year Final Research Report
Structure analysis of mutant SOD1 and ALS immunotherapy using new monoclonal antibodies
| 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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| Keywords | ALS / SOD1 / 免疫療法 / モノクローナル抗体 / 構造解析 |
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| 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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[Journal Article] Aberrant Assembly of RNA-Recognition Motif 1 Links to Pathogenic Conversion of TAR DNA-binding protein 43 (TDP-43)2013
Author(s)
Shodai A., Morimura T., Ido A., Uchida T., Ayaki T., Takahashi R., Kitazawa S., Suzuki S., Shirouzu M., Kigawa T., Muto Y., Yokoyama S., Takahashi R., Kitahara R., Ito H., Fujiwara N., Urushitani M
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Journal Title
J. Biol. Chem
Volume: 288
Pages: 14886-14905
DOI
Peer Reviewed
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[Presentation] Oxidation of Cys111 residue in loop VI of human copper/zinc superoxide dismutase2011
Author(s)
Fujiwara N., Ihara K., Kato S., Yoshihara D., Eguchi H., Sakiyama H., Wakatsuki S., Taniguchi N. and Suzuki K
Organizer
12th Int. Congress on Amino Acids, Peptides and Proteins, Beijing 2011
Place of Presentation
Beijing, China
Year and Date
20110801-05
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