| Project/Area Number |
16390104
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Niigata University |
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Principal Investigator |
TAKAHASHI Hitoshi Niigata University, Brain Research Institute, Professor, 脳研究所, 教授 (90206839)
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| Co-Investigator(Kenkyū-buntansha) |
TOYOSHIMA Yasuko Niigata University, Brain Research Institute, Assistant, 脳研究所, 助手 (20334675)
YAMADA Mitsunori Niigata University, Brain Research Institute, Associate Professor, 脳研究所, 助教授 (30240039)
ONODERA Osamu Niigata University, Brain Research Institute, Associate Professor, 脳研究所, 助教授 (20303167)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2004: ¥3,500,000 (Direct Cost: ¥3,500,000)
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| Keywords | Spinocerebellar ataxia / 1C2 / polyglutamine diseases / Western blotting / Two-dimensional electrophoresis / amino acid sequence / 小脳変性症 / ウェスタンブロッティング |
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| Research Abstract |
We have studied three patients with pathologically different hereditary spinocerebellar ataxia characterized by 1C2-immunopositive intranuclear inclusions in the affected CNS neurons, namely, polyglutamine diseases. We have also tried to identify the gene responsible for each hereditary disease.
(1)We have described a homozygous case of spinocerebellar ataxia type 17 with 48 glutamines. The age of the patient at disease onset was lower than those of heterozygotes with the same CAG-repeat sizes, but the clinical manifestations were rapidly progressive dementia and chorea. Neuronal loss was relatively restricted and most prominent in the Purkinje cell layer and striatum ; however, intranuclear neuronal polyglutamine accumulation was widespread, with a high frequency in the cerebral cortex and striatum.
(2)In one of the other two cases, immunoblotting analyses with a monoclonal antibody specific for expanded polyglutamine stretches (1C2) revealed the presence of immunopositive proteins. Furthermore, we identified multiple spots, one of which might be the disease-related protein, using two-dimensional electrophoresis and two-dimensional immunoblotting methods. Further studies are needed to identify the gene responsible for the disease.
(3)In the final case, we are trying the same methods to identify the disease-related protein and the causative gene abnormality.
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