| Project/Area Number |
18590926
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Gunma University |
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Principal Investigator |
OKAMOTO Koichi Gunma University, Department of Neurology, Graduate School of Medicine, Professor (00124652)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUNO Yuji Gunma University, School of Medicine, Department of Neurology, Assistant Professor (20282395)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Parkinson's disease / amyotrophic lateral sclerosis / Golgi apparatus / TDP-43 / Lewy body / 神経病理 / ゴルジ装置 / トランスフェリン / シスタチンC / 神経変性疾患 / 中脳 |
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| Research Abstract |
We examined whether the Golgi apparatus (GA) is fragmented in nigral neurons in Parkinson's disease (PD). We did not observe fragmented GA in nigral neurons in contoro cases by immunocytochemistry with an anti-TGN46 antibody. In PD, the GA was fragmented in 3% of the nigral neurons without inclusions, and in 5% of the neurons with Lewy bodies. In contrast, fragmented GA was noted in 19% of the neurons containing pale bodies. Since pale bodies represent early stages in the development of brainstem Lewy bodies, our results suggest that the cytotoxicity of alpha-synuclein-positive aggregates is reduced in the process of Lewy body formation. Transferrin, an iron-binding protein, plays an important role in the transport and delivery of circulating ferric iron to the tissues. We demonstrated that transferrin localized in Bunina bodies and some of the basophilic inclusions in ALS cases. In contrast, skein-like inclusions and Lewy body-like inclusions or round inclusions did not show obviously detectable transferrin immunoreactivities. Recently, TDP-43 was identified as a major component of ubiquitinated neuronal cytoplasmic inclusions observed in lower motor neurons in ALS and frontotemporal lobar degeneration with ubiquitinated inclusions. Almost all of the anterior horn cells with abnormal TDP-43 immunoreactivities showed GA fragmentation. These results suggest that neurons with abnormal TDP-43 immunoreactivities are associated with dysfunction of the secretory pathway in motor neurons in ALS.
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