| Project/Area Number |
02670515
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | Osaka University |
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Principal Investigator |
TAKEDA Masatoshi Osaka University Medical School Assistant Professor, 医学部, 講師 (00179649)
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| Co-Investigator(Kenkyū-buntansha) |
TADA Kunitoshi Osaka University Medical School Assistant Professor, 医学部, 講師 (80135681)
HARIGUCHI Shiro Osaka University Medical School Associate Professor, 医学部, 助教授 (10028459)
NISHIMURA Tsuyoshi Osaka University Medical School Professor, 医学部, 教授 (70028455)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1990: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Alzheimer's Disease / fibroblast / vimentin / fodrin / intermediate Filament / calcium / protease / ubiquitin / 中間径線維 / ユピキチン / 家族性 / 細胞骨格蛋白 / 皮膚 |
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| Research Abstract |
The fibroblasts were cultured from the cutaneous tissue of patients with familial Alzheimer's disease and non-familial Alzheimer's disease. In the process of collecting many clones of fibroblasts, a clone with a mutation in amyloid beta-protein precursor gene was found. The mutation was the same as reported by Goat et al, i. e. a substitution of Val to Ile at 717 of amyloid beta-protein precursor. The distribution of vimentin fibers in the cultured fibroblasts were studied, showing the drastic derangement in vimentin distribution in Alzheimer cells. The derangement was most obviously noticed with the cells with the mutation. The vimentin molecule showed no changes but the fodrin showed the increased accumulation in fibroblasts from Alzheimer patients. It was found that fodrin degradation in Alzheimr cells is inhibited. Considering the possibility that fodrin is degraded by Calcium-activated neutral protease (CANP), the calcium level and mobilization in Alzheimer cells was investigated. The results showed that calcium mobilization is significantly suppressed in Alzheimer fibroblasts. It is highly speculated that metabolism of cytoskeletal proteins such as fodrin is altered in Alzheimer cells which is closely related with the pathological processes observed in Alzheimer brain.
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