Analyses of the nuclear protein that aggregates in brains of patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration
Project/Area Number |
19591024
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurology
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Research Institution | Tokyo Metropolitan Organization for Medical Research |
Principal Investigator |
ARAI Tetsuaki Tokyo Metropolitan Organization for Medical Research, 東京都精神医学総合研究所, 主任研究員 (90291145)
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Co-Investigator(Kenkyū-buntansha) |
長谷川 成人 東京都精神医学総合研究所, 副参研究員 (10251232)
|
Co-Investigator(Renkei-kenkyūsha) |
HASEGAWA Masato 財団法人東京都医学研究機構, 東京都精神医学総合研究所, 副参事研究員 (10251232)
|
Project Period (FY) |
2007 – 2009
|
Project Status |
Completed (Fiscal Year 2009)
|
Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 封入体 / 神経変性疾患 / 認知症 / 運動障害 / リン酸化 / 人格変化 |
Research Abstract |
TAR DNA-binding protein of M_r 43 kDa (TDP-43) is a major component of the tau-negative and ubiquitin-positive inclusions that characterize amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration which is now referred to as FTLD-TDP. Concurrent TDP-43 pathology has been reported in a variety of other neurodegenerative disorders such as Alzheimer's disease, forming a group of TDP-43 proteinopathy. Accumulated TDP-43 is characterized by phosphorylation and fragmentation. There is a close relationship between the pathological subtypes of FTLD-TDP and the immunoblot pattern of the C-terminal fragments of phosphorylated TDP-43. These results suggest that proteolytic processing of accumulated TDP-43 may play an important role for the pathological process. In cultured cells, transfected C-terminal fragments of TDP-43 are more prone to form aggregates than full-length TDP-43. Understanding the mechanism of phosphorylation and truncation of TDP-43 and aggregate formation may be crucial for clarifying the pathogenesis of TDP-43 proteinopathy and for developing useful therapeutics.
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Report
(4 results)
Research Products
(126 results)
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[Journal Article] The 28-amino acid form of an APLP1-derived Aβ-like peptide is a surrogate marker for Aβ42 production in the central nervous system2009
Author(s)
Yanagida K, Okochi M, Tagami S, Nakayama T, Kodama TS, Nishitomi K, Jiang J, Tatsumi S, Mori K, Tatsumi S, Arai T, 他17名
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Journal Title
EMBO Molecular Medicine (印刷中)
Related Report
Peer Reviewed
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[Journal Article] TDP-43 in ubiquitinated inclusions in the inferior olives in frontotemporal lobar degeneration and in other neurodegenerative diseases : a degenerative process distinct from normal ageing2009
Author(s)
Davidson Y, Amin H, Kelley T, Shi J, Tian J, Kumaran R, Lashley T, Lees AJ, Duplessis D, Neary D, Snowden J, Akiyama H, Arai T, 他5名
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] Metastatic CNS lymphoma presenting with periventricular dissemination-MRI and neuropathological findings in an autopsy case2009
Author(s)
Kobayashi Z, Tsuchiya K, Machida A, Goto J, Yokota O, Miake H, Watabiki S, Taki K, Ishizu H, Haga C, Arai T, 他2名
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Journal Title
J Neurol Sci 277
Pages: 109-113
Related Report
Peer Reviewed
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