2003 Fiscal Year Final Research Report Summary
Multiple approaches of the therapy for lysosomal diseases affected with central nervous system
| 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 Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30314313)
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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)
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| Project Period (FY) |
2001 – 2003
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| Keywords | lysosomal disease / psychosine / T cell death associated gene 8 / Krabbe disease / Farber disease / saposin A / Molecular shaperon |
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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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Research Products
(14 results)
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[Publications] Inui K, Akagi M, Ono J, Tsukamoto H, Shimono K, Mano T, Imai K, Yamada M, Muramatsu T, Sakai N, Okada S: "Mutational analysis of MECP2 in Japanese patients with atypical Rett syndrome"Brain Dev.. 23(4). 212-215 (2001)
Description
「研究成果報告書概要(和文)」より
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[Publications] Kokubu C, Wilm C, Kokubu T, Walil M, Rodrigo I, Sakai N, Santagati F, Hayashizaki Y, Suzuki M, Yamamura K, Abe K, Imai K: "Undulated short-tail Deletion Mutation in the Mouse Ablates Paxi and Leads to Ectopic Activation of Neighboring NkxZ-2 in Domains that Normally Express Pax1"Genetics. 165. 299-307 (2003)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Inui K, Akagi M, Ono J, Tsukamoto H, Shimono K, Mano T, Imai K, Yamada M, Muramatsu T, Sakai N, Okada S: "Mutational analysis of MECP2 in Japanese patients with atypical Rett syndrome"Brain Dev.. 23(4). 212-215 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Inui K, Yanagihara K, Otani K, Suzuki Y, Akagi M, Nakayama M, Ida H, Okada S.: "A new variant neuropathic type of Gauchefs disease characterized by hydrocephalus, corneal opacities, deformed toes, and fibrous thickening of spleen and liver capsules."J Pediatr.. 138(1). 137-139 (2001)
Description
「研究成果報告書概要(欧文)」より
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