| Project/Area Number |
13470164
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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 |
Pediatrics
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| Research Institution | Osaka University |
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Principal Investigator |
SAKAI Norio (2003) Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30314313)
乾 幸治 (2001-2002) 大阪大学, 医学系研究科, 助教授 (90175208)
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| Co-Investigator(Kenkyū-buntansha) |
WADA Kazuko Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30294094)
平野 慎也 大阪大学, 医学部附属病院, 医員(臨床研究)
酒井 規夫 大阪大学, 医学系研究科, 助手 (30314313)
島 雅昭 大阪大学, 医学系研究科, 講師 (10252660)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥8,900,000 (Direct Cost: ¥8,900,000)
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| Keywords | lysosomal disease / psychosine / T cell death associated gene 8 / Krabbe disease / Farber disease / saposin A / Molecular shaperon / ガラクトセレブロシダーゼ / 遺伝子変異解析 / 蛋白質発現系 / DHPLC法 |
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| Research Abstract |
Lysosomal diseases were caused by the accumulation of undigested substrates within lysosome. The lysosomal diseases affected in the central nervous system were hard to treat because the recombinant enzyme could not be entered through blood brain barrier. We tried several projects to approach the therapy of these disease, as follows ;
1)Express affected enzyme: We tried to construct for the normal galactocerebrosidase to express in large-scale in yeast, however the ratio of expression was not good enough.
2)Inhibition of synthetic enzyme of sphingolipid : We realize that cycloserine was confirmed to inhibit production of psychosine. We will check dose dependency for the effect of cycloserine.
3)Molecular shaperon : Saposine A was proven to be the activator of galactocerebrosidase and might be shaperon for it. We were succeeded in express saposin A in yeast expression system. Purified saposin A was able to activate β-glucosidase and galactocerebrosidase.
4)Activation of affected enzyme: The produced saposin A might be able to bind enzyme and stabilyze them. We are analyzing this effect in vivo.
5)Block apoptosis cascade : We check the expression profile of TDAG8 and analyzed the effect of antibody against TDAG8.
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