The aggregation mechanism of TDP-43 protein
| Project/Area Number |
16K21650
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurophysiology / General neuroscience
Cell biology
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
SUZUKI Genjiro 公益財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野, 主席研究員 (60466034)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | ALS / TDP-43 / プリオン / 神経変性疾患 / 筋委縮性側索硬化症 |
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| Outline of Final Research Achievements |
In neurodegenerative diseases, accumulation of abnormal proteins in cells in the brain is a widespread phenomenon and is considered to be the cause of neuronal degeneration. Abnormal aggregations of TDP-43 are observed in neurons of amyotrophic lateral sclerosis (ALS) patients and frontotemporal lobar degeneration (FTLD) patients, thus, these aggregations may be the cause of these diseases. In this study, abnormal aggregates were made from TDP-43 monomer synthesized in vitro, and the accumulation process of abnormal TDP-43 aggregates could be observed in detail in the human neurofibroblast SH-SY5Y cell line. We also found that accumulated TDP-43 is aberrantly phosphorylated in the same way as the patient's brain.
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| Academic Significance and Societal Importance of the Research Achievements |
筋萎縮性側索硬化症（ALS）や前頭側頭葉変性症（FTLD）などの神経変性疾患ではTDP-43というタンパク質が神経細胞において異常に凝集していることが観察されており、これらの疾患の原因であると考えられる。本研究により試験管内で合成したTDP-43タンパク質の異常凝集によりヒト神経線維芽細胞において異常TDP-43凝集体の蓄積を誘導することができた点は、これらの疾患の細胞モデルの確立へとつながり、学術的かつ社会的に意義が高いものであると考えられる。今後、マウスなどの動物モデルに応用することにより、有効な動物モデルの確立や、治療薬の開発への応用も期待できる。
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] Phosphorylation of TAR DNA-binding Protein of 43 kDa (TDP-43) by Truncated Casein Kinase 1δ Triggers Mislocalization and Accumulation of TDP-43.2016
Author(s)
Nonaka T, Suzuki G, Tanaka Y, Kametani F, Hirai S, Okado H, Miyashita T, Saitoe M, Akiyama H, Masai H, Hasegawa M.
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Journal Title
J Biol Chem
Volume: 291
Issue: 17
Pages: 8896-907
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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