| Project/Area Number |
25640029
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Nagasaki University |
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Principal Investigator |
ATARASHI Ryuichiro 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (90452846)
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| Co-Investigator(Renkei-kenkyūsha) |
SATOH Katsuya 長崎大学, 医歯薬学総合研究科(保健学科), 教授 (70398147)
SANO Kazunori 福岡大学, 薬学部, 講師 (50534343)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | レビー小体型認知症 / alpha-synuclein / オリゴマー / アミロイドフィブリル / 神経変性疾患 |
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| Outline of Final Research Achievements |
The molecular basis of seed-dependent aggregation of alpha-synuclein (aSyn) in the pathogenesis of dementia with Lewy bodies (DLB) remains unclear. We investigated whether brain tissues from DLB, which contain serine 129 (Ser129) phosphorylated insoluble aggregates of aSyn, can convert recombinant aSyn (r-aSyn) to amyloid fibrils using real-time quaking-induced conversion (RT-QUIC). Diffuse neocortical DLB type yielded 50% seeding dose (SD50) values of 107-8/g brain. The SD50 of Limbic DLB type was about 105/g brain. Further studies found that RT-QUIC assay was able to discriminate DLB from other neurodegenerative disorders. Of note, the seeding activity was reconstructed in reactions seeded with soluble r-aSyn oligomers, but not with insoluble r-aSyn aggregates, regardless its Ser129 phosphorylation status. These findings suggest that RT-QUIC using r-aSyn as a substrate can be applied to detect the pathogenic aSyn fibrils in DLB, and the potential culprit is oligomeric forms of aSyn.
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