An attempt to elucidate a biomarker for the diagnosis of amyotrophic lateral sclerosis
| Project/Area Number |
23659309
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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 |
Laboratory medicine
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| Research Institution | Nihon University |
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Principal Investigator |
ONO Shinichi 日本大学, 薬学部, 教授 (20246862)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Utaka 日本大学, 医学部, 准教授 (10287625)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2011: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
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| Keywords | 銅イオン / Ammonium tetrathiomolybdate / 変異SOD1 / 銅イオンキレート / テトラチオモリブデン酸 / 筋萎縮性側索硬化症 / バイオマーカー |
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| Research Abstract |
Using the mouse strains G127TGGG (G127X), G85R, D90A, and G93A, which express SOD1 mutants with different copper-binding abilities, we showed that copper dyshomeostasis is common to these SOD1 mutants. Copper contents bound to the SOD1 active site varied considerably between SOD1 mutants: G93A and D90A SOD1 mutants have higher affinity to copper ions at their active site, whereas the affinity to copper ions are lower in G127X and G85R SOD1 mutants. Irrespective of the affinity, all the SOD1 mutants upregulated Steap2, Ctr1, Cox17, and Atox1, and downregulated Atp7a, which resulted in copper accumulation in spinal cords of the mice. We propose that copper dyshomeostasis is common to SOD1 mutation-linked ALS, and could be useful as a biological marker for the diagnosis.
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Report
(3 results)
Research Products
(22 results)
