Identification of chemical compounds inhibiting SOD1-Derlin-1 interaction for ALS treatment
| Project/Area Number |
26650028
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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 |
Functional biochemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Homma Kengo 東京大学, 薬学研究科(研究院), 助教 (60708171)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ALS / SOD1 / 低分子化合物 / PPI阻害 / PPI阻害剤 / Derlin-1 |
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| Outline of Final Research Achievements |
ALS is a devastating neurodegenerative disease characterized by the selective motoneuron death. We have previously reported that more than 100 different SOD1 mutants specifically interact with Derlin-1, a component of ERAD machinery. This interaction cause ER stress, leading to the motoneuron death. Motoneuron death induced by SOD1 mutants was significantly attenuated by coexpression of a SOD1-Derlin-1 interaction inhibitory peptide, suggesting that this interaction plays an important role in the pathogenesis of ALS. Therefore, the low molecular weight compounds inhibiting SOD1-Derlin-1 interaction can be used as the novel therapeutic approach for ALS.
Here we screened about 160,000 chemical compounds. Continuous intraventricular administration of one prominent inhibitor has ameliorated disease in a mouse model of ALS, delayed onset significantly and prolonged survival. Our results show the possibilities to establish ALS treatment based on the molecular mechanism.
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Report
(3 results)
Research Products
(5 results)
