2017 Fiscal Year Final Research Report
Development of a novel molecular targeting therapy and probe, using antibodies against pathogenic epitopes in TDP-43
| Project/Area Number |
26290023
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Shiga University of Medical Science (2016-2017)
Kyoto University (2014-2015) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
守村 敏史 滋賀医科大学, 神経難病研究センター, 助教 (20333338)
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Keywords | 筋萎縮性側索硬化症（ALS) / ミスフォールドプロテイン / 神経変性疾患 / 抗体医療 / 蛋白質分解 |
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| Outline of Final Research Achievements |
Using our original antibodies against TDP-43, a pathogenic protein for amyotrophic lateral sclerosis, we tested their utility as a tool for high throughput drug screening, and as a specific scavenger of pathogenic TDP-43 aggregates in cells.
For high throughput screening, a polyclonal antibody against dimer interface residues in RRM1 domain, was used in the competitive ELISA, in which molecules which prevents antibody binding with TDP-43 were screening as a hit molecules.Screening worked and several hits were picked up, which interacted dimer interface and efficiently prevents aggregate formation in the transfected culture cells.
To eliminate intracellular TDP-43 aggregates, several types of single chain fragment of variant (scFV) containing proteolysis signals, were generated. These scFv were transfected with normal or aggregate-prone TDP-43. It was shown that our scFv was a promising tool to eliminate misfolded and pathogenic TDP-43 in ALS.
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| Free Research Field |
神経変性疾患
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