elucidation of pathomechanism in sporadic ALS
| Project/Area Number |
22590965
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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 | Tokyo Women's Medical University |
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Principal Investigator |
SASAKI SHOICHI 東京女子医科大学, 医学部, 准教授 (40119962)
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| Project Period (FY) |
2010-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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| Keywords | 筋萎縮性側索硬化症 / オートファジー / TDP-43 ノックアウトマウス / AMPA 受容体 / RNA 編集 / ADAR2-ノックアウトマウス / カルシウム / 血液-脊髄関門 / コンディショナルTDP-43ノックアウトマウス / 血液ー脊髄関門 / 癒着帯 / フィブリノーゲン / 超微細構造 / ADAR2-knockout マウス / AMPA受容体 / autolysosome / autophagosome / LC3 / p62 / 運動ニューロン疾患 / GluA2 / コンデショナルADAR2ノックアウトマウス / 核内空胞変化 / 病理 / P62 / 電子顕微鏡 / TDP-43 / 粗面小胞体 / ミトコンドリア |
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| Outline of Final Research Achievements |
(1) In amyotrophic lateral sclerosis (ALS), TDP-43 trafficking between the nucleus and the cytoplasm is disturbed, resulting in an accumulation of TDP-43 in the cytoplasm in the form of insoluble aggregates. (2) Autophagy is significantly activated in the cytoplasm of motor neurons in sporadic ALS and may be involved in the pathomechanism of the neurodegeneration of motor neurons. (3) ADAR2-reduction is associated with progressive deterioration of nuclear architecture, resulting in vacuolated nuclei due to a Ca2+-permeable AMPA receptor-mediated mechanism. (4) Significantly increased autophagy flux in the degenerating motor neurons of ADAR2-knockout mice likely resulted from Ca2+ overload. (5) The temporary and reversible breakdown of the blood-spinal cord barrier at the early symptomatic stage could be a direct pathogenic consequence of the loss of TDP-43 protein in TDP conditional knockout mice.
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Report
(6 results)
Research Products
(29 results)
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[Journal Article] Optineurin is co-localized with FUS in basophilic inclusions of ALS with FUS mutation and in basophilic inclusion body disease2011
Author(s)
Ito H, Fujita K, Nakamura M, Wate R, Kaneko S, Sasaki S, Yamane K, Suzuki N, Aoki M, Shibata N, Togashi S, Kawata A, Mochizuki Y, Mizutani T, Maruyama H, Hirano A, Takahashi R, Kawakami H, Kusaka H
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Journal Title
Acta Neuropathologica
Volume: 121
Issue: 4
Pages: 555-557
DOI
Related Report
Peer Reviewed
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