| Budget Amount *help |
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2017: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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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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