| Project/Area Number |
20390250
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | National Center of Neurology and Psychiatry |
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Principal Investigator |
NISHINO Ichizo National Center of Neurology and Psychiatry, ・神経研究所疾病研究第一部, 部長 (00332388)
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| Co-Investigator(Kenkyū-buntansha) |
NOGUCHI Satoru 独立行政法人 国立精神・神経医療研究センター, 神経研究所疾病研究第一部, 室長 (00370982)
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| Co-Investigator(Renkei-kenkyūsha) |
HAYASHI Yukiko 独立行政法人 国立精神・神経医療研究センター, 神経研究所疾病研究第一部, 室長 (50238135)
NONAKA Ikuya 独立行政法人 国立精神・神経医療研究センター, 病院, 名誉院長 (80040210)
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| Research Collaborator |
HONDA Shinya 独立行政法人 国立精神・神経医療研究センター, 神経研究所疾病研究第一部, 流動研究員
TOMINAGA Kayo 独立行政法人 国立精神・神経医療研究センター, 神経研究所疾病研究第一部, 研究生
MONMA Kazunari 独立行政法人 国立精神・神経医療研究センター, 神経研究所疾病研究第一部, 研究生
KIYONO Chieko 独立行政法人 国立精神・神経医療研究センター, 病院, レジデント
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2010: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2009: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2008: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
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| Keywords | 神経分子病態学 / 筋疾患 / オートファジー / 神経分子病態 |
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| Research Abstract |
To elucidate the pathomechanism of and to develop the therapy of autophagy-related muscle disorders, we physiologically and pathologically characterized the phenotypes of skeletal and cardiac muscles from Lamp-2 knock-out mice, a model mouse for Danon disease, and analyzed the recovery of phenotype by exogenous expression of the Lamp-2 homolog, Lamp-1. By cross-mating with Lamp-1 overexpressing mouse, cardiac functions was recovered in Lamp-2 knock-out mice. In Lamp-2 deficient cells, degradation by macroautophagy was remarkably decreased. This decrease was corrected by Lamp-1 overexpression. Most likely, Lamp-1 overexpression improves the fusion between autophagosomes and lysosomes, and ameliorates the cell dysfunction caused by Lamp-2 deficiency. Overall, induction of Lamp-1 expression may be a good candidate for the development of therapy for Danon disease.
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