2012 Fiscal Year Final Research Report
Roles of excitotoxicity in pathogenesis of degenerative neurological diseases
| Project/Area Number |
22390173
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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 |
Neurology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KWAK Shin 東京大学, 大学院・医学系研究科, 客員研究員 (40160981)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 神経変性疾患 / 筋萎縮性側索硬化症 / 封入体 / TDP-43 / AMPA 受容体 / カルシウム / カルパイン |
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| Research Abstract |
Presence of intracellular inclusion body is a pathological hallmark of degenerative neurological diseases but how these inclusions are formed is largely unknown. TDP-43 is a composite protein of inclusions seen in motor neurons of amyotrophic lateral sclerosis (ALS) and cortical neurons of frontotemporal lobar degeneration (FTLD) patients. We found that calcium-dependent cysteine protease calpain specifically cleaved C-terminal regions of TDP-43, thereby generating aggregation-prone fragments. We did not find α-synuclein-, Aβ-, or tau-containing inclusions in the mutant mice with abnormal calcium signaling.
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