| Project/Area Number |
17590873
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Kanazawa Medical University |
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Principal Investigator |
MATSUI Masaru Kanazawa Medical University, Medicine, senior assistant professor, 医学部, 講師 (60378750)
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| Co-Investigator(Kenkyū-buntansha) |
TOMIMOTO Hidekazu Kyoto University, Graduate School of Medicine, senior assistant professor, 医学研究科, 講師 (80324648)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | cerebral white matter / leukoencephalopathy / eIF2B / Binswanger disease / GFAP / astrocyte / vanishing / eIF2α / 大脳白質 |
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| Research Abstract |
Recently, mutations in the genes encoding the subunits of the eukaryotic translation initiation factor 2B (eIF2B) have been identified as the cause of leukoencephalopathy with vanishing white matter (VWM). EIF2B plays an important role in the regulation of translation initiation of protein synthesis. We identified a novel EIF2B mutation in adult-onset VWM. We hypothesized the abnormality of eIF in Binswanger disease may cause the white matter lesions of Binswanger disesase.
We used a total number of 16 cases constituting of 5 age matched control, 5 patients with Binswanger disease, 6 other disease. We used the section from the cerebral white matter.
Immunohistochemistry by using ABC method were performed. The number of GFAP positive cell showed no significant difference between Binswanger group and normal control. On the other hand, We identified the increased number of the phosphorylated eIF2α positive astrocytes in the cerebral white matter lesion in Binswanger disease. EIF2α is a competitive inhibitor of eIF2B. Therefore, we hypothesized that phosphorylation of eIF2α, dysfunction of eIF2B, reduced mRNA translation and dysfunction of astrocytes may be the cause of white matter damage of Binswanger disease. We further examined the expression of CREB-2, GADD, phosphorylated GCN-2, phosphorylated MAPK in the autopsied brains and the animal model of chronic ischemia. We did not get the significant difference.
We need a further research to identify the molecular mechanism of the formation of the cerebral white matter lesion of Binswanger disease.
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