Molecular mechanism underlying propagation of pathogenic protein aggregates in neurodegenerative disorders
| Project/Area Number |
15H06588
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|---|
| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
|---|
| Research Field |
Functional biochemistry
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| Research Institution | Keio University |
|---|
Principal Investigator |
Eiichi Tokuda 慶應義塾大学, 理工学部(矢上), 助教 (00757510)
|
|---|
| Project Period (FY) |
2015-08-28 – 2017-03-31
|
| Project Status |
Completed (Fiscal Year 2016)
|
| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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|---|
| Keywords | 筋萎縮性側索硬化症 / タンパク質凝集体 / シーディング / 線虫 / スーパーオキサイド ディスムターゼ / 神経変性疾患 / タンパク質線維 |
|---|
| Outline of Final Research Achievements |
Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. The disease begins focally and spreads contiguously, resulting in progressive paralysis. The pathological hallmark of ALS is the accumulation of insoluble protein aggregates containing Cu/Zn-superoxide dismutase (SOD1) in motor neurons. The aim of this project was to clarify a molecular mechanism underlying the spread of lesion sites in the disease from the viewpoint of seeding activity of insoluble SOD1 aggregates. I first established two different methods: oral intake of E.coli forming the aggregates by thermoregulation, and exposure of the purified aggregates. Although transgenic C.elegans harboring human SOD1 were fed with the aggregates, feeding with either E.coli forming the aggregates or the purified aggregates did not induce the aggregation of human SOD1 in C.elegans. Furthermore, these aggregates did not affect overall lifespan and motor function of C.elegans.
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Report
(3 results)
Research Products
(12 results)
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[Journal Article] Regulatory Role of RNA Chaperone TDP-43 for RNA Misfolding and Repeat-Associated Translation in SCA312017
Author(s)
Taro Ishiguro, Nozomu Sato, Morio Ueyama, Nobuhiro Fujikake, Chantal Sellier, Akemi Kanegami, Eiichi Tokuda, Bita Zamiri, Terence Gall-Duncan, Mila Mirceta, Yoshiaki Furukawa, 他８名
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Journal Title
Neuron
Volume: 94
Issue: 1
Pages: 108-124
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Immunochemical characterization on pathological oligomers of mutant Cu/Zn-superoxide dismutase in amyotrophic lateral sclerosis2017
Author(s)
Tokuda E, Anzai I, Nomura T, Toichi K, Watanabe M, Ohara S, Watanabe S, Yamanaka K, Morisaki Y, Misawa H, and Furukawa Y.
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Journal Title
Molecular Neurodegeneration
Volume: 12
Pages: 2-2
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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