| Project/Area Number |
20240037
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Niigata University |
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Principal Investigator |
TAKAHASHI Hitoshi Niigata University, 脳研究所, 教授 (90206839)
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| Co-Investigator(Kenkyū-buntansha) |
TAN ChenーFeng 新潟大学, 脳研究所, 助教 (40447610)
TOYOSHIMA Yasuko 新潟大学, 脳研究所, 助教 (20334675)
ONODERA Osamu 新潟大学, 脳研究所, 准教授 (20303167)
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| Co-Investigator(Renkei-kenkyūsha) |
KAKITA Akiyoshi 新潟大学, 脳研究所, 准教授 (80281012)
SAKIMURA Kenji 新潟大学, 脳研究所, 教授 (40162325)
KUWANO Ryozo 新潟大学, 脳研究所, 教授 (20111734)
YOKOYAMA Minesuke 新潟大学, 脳研究所, 教授 (40090930)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥37,440,000 (Direct Cost: ¥28,800,000、Indirect Cost: ¥8,640,000)
Fiscal Year 2010: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Fiscal Year 2009: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
Fiscal Year 2008: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
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| Keywords | 神経変性疾患 / 筋萎縮性側索硬化症 / TDP-43 / 臨床病理 / 免疫組織化学 / 封入体 / 分子病理 / 分子生物学 / 人口呼吸 / 封人体 |
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| Research Abstract |
We examined clinicopathologically and immunohistochemically a large series of sporadic amyotrophic lateral sclerosis (SALS) cases, including those having long disease durations with artificial respiratory support. In each case, various brain regions were immunostained with an antibody against TDP-43, showing occurrence of TDP-43-positive neuronal (NCIs) and glial cytoplasmic inclusions in many regions, including the lower motor neuron nuclei. The results obtained indicate that SALS is a multisystem neuro-glial proteinopathy of TDP-43 and can show two pathological phenotypes (types 1 and 2 ; type 2 can be distinguished from type 1 by the presence of TDP-43-positive NCIs in the frontotemoral cortex, hippocampal formation, neostriatum and substantia nigra). We also generated a transgenic TDP-43 KO mouse model for further biochemical and molecular analyses on the pathomechanisms underlying SALS. The several data obtained strongly suggest that our next target is "splicing abnormalities of TDP-43".
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