| Project/Area Number |
26461287
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Department of Clinical Research, National Hospital Organization Utano National Hospital |
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Principal Investigator |
Yamamoto Kenji 独立行政法人国立病院機構(宇多野病院臨床研究部), その他部局等, 研究員(移行) (50378775)
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| Co-Investigator(Kenkyū-buntansha) |
澤田 秀幸 独立行政法人国立病院機構(宇多野病院臨床研究部), その他部局等, その他 (30335260)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
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| Keywords | αシヌクレイン / パーキンソン病 / レビー小体型認知症 / IP3受容体 / カルシウム遊離 / カルシウム結合蛋白 / オリゴマー / カルシウムチャンネル / カルシウム / 小胞体 / 神経変性 / 膜興奮性 / シナプス伝達 |
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| Outline of Final Research Achievements |
α-Synuclein oligomers and dysregulated activity-dependent Ca2+ homeostasis play pivotal roles in the selective neuronal damage occurring in Lewy body disease. The current study used electrophysiological and immunochemical analyses to evaluate how intracellular α-synuclein oligomers act on the neuronal excitability and Ca2+ dynamics in neocortical pyramidal neurons. Intracellularly applied higher-order α-synuclein oligomers directly capture calcium-binding protein 1, a negative regulator of inositol trisphosphate receptor (IP3R) gating, and cause the aberrant form of Ca2+-induced Ca2+ release from IP3R during multiple spikes. This is a non- physiological action in neocortical neurons and is blocked by L-type Ca2+ channel blockers. This oligomeric α-synuclein-mediated mechanism may cause intracellular Ca2+ dysregulation and could be the molecular basis for neuronal vulnerability in Lewy body disease.
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