| Project/Area Number |
16590848
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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 | Juntendo University |
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Principal Investigator |
MORI Hideo Juntendo University, Dept.Neurol, Associate Prof, 医学部, 助教授 (30150634)
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| Co-Investigator(Kenkyū-buntansha) |
TADA Nobuhiro JUNTENDO UNIVERSITY, Graduate School of medicine, assistant Prof, 医学部, 講師 (50338315)
SHIMURA Hideki JUNTENDO UNIVERSITY, School of medicine, Aassistant, 医学部, 助手 (50286746)
石黒 幸一 三菱科生命研, 生命分子工学部, 主任研究員 (50374012)
KOBAYASHI Tomonori Fukuoka University, School of medicine, assistant, 医学部, 助手 (50266053)
本井 ゆみ子 順天堂大学, 医学部, 助手 (60338407)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | tauopathy / frontotemporal dementia / parkinsonism / tau protein / phosphorylated / corticobasal degeneration / N279 / パーキンソン病 / タウ蛋白 / 遺伝子改変動物 / トランスジェニックマウス / 培養細胞 / 認知症 / 異常りん酸化 / 神経原線維変化 / 痴呆 |
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| Research Abstract |
1)Based on the analysis of the clinical, pathological and genetic features of the three families with tau N279K mutation, we have demonstrated that the clinical phenotype of N279K mutation was relatively uniform even in the families with unrelated founders. The pathologic changes involved the spinal cord as well as basal ganglia, and cerebral cortex and white matter.
2)We have retrospectively reviewed 8 patients with autopsy-proven corticobasal degeneration and reported the variable clinical phenotypes including marked palilalia, progressive dysarthria, progressive dysphagia, and non-fluent aphasia.
3)We transiently transfected mouse neuroblastoma cells (N18TG2) with wild-type tau or tau with the L266V mutation from a patient with familial frontotemporal dementia. Tau protein was observed in both the wild-type and L266V mutant tau transfectants, as were inclusions composed of tau phosphorylated at amino acids Thrl 81, Ser 202/Thr205, and Ser396. Inclusions immunoreactive with anti-tau antibodies AT8 and pS396 were also immunoreactive with antibodies against ubiquitin and glycogen synthase kinase 3□.
4)We have revealed that progression of motor deterioration in the model mice with P301 tau mutation was inhibited by administration of lithium.
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