2006 Fiscal Year Final Research Report Summary
PATHOGENIC MECHANISM OF CONGENITAL ANOMALY AND LIFE-STYLE RELATED DISEASES BASED ON PEROXISOMAL METABOLISM
| Project/Area Number |
17591079
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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 |
Pediatrics
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| Research Institution | Gifu University |
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Principal Investigator |
SHIMOZAWA Nobuyuki GIFU UNIVERSITY, LIFE SCIENCE RESEARCH CENTER, DIVISION OF GENOMICS RESEARCH, PROFESSOR, 生命科学総合研究支援センター, 教授 (00240797)
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| Co-Investigator(Kenkyū-buntansha) |
ORII Koji GIFU UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PART-TIME LECTURER, 医学系研究科, 非常勤講師 (30377668)
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| Project Period (FY) |
2005 – 2006
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| Keywords | PEROXISOME / FATTY ACID β-OXIDATION / LIFE-STYLE RELATED DISEASE / SCREEN SYSTEM OF PEROXISOMAL DISEASES |
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| Research Abstract |
(1) We have established a diagnostic system of peroxisomal diseases in Japan, and have identified 40 Japanese with peroxisomal biogenesis disorders (PBD), 11 patients with beta-oxidation enzyme deficiencies and more than 100 patients with X-linked adrenoleukodystrophy (ALD).
(2) The national history of ALD was investigated, using a nation-wide retrospective study based on a questionnaire survey. The data on 145 patients, including 46 patients with the childhood cerebral form, 39 with adrenomyeloneuropathy (AMN), 33 with the adult cerebral form, 14 with the adorescent form and 13 with the olivo-ponto-cerebellar (OPC) form, were analyzed.
(3) We demonstrated Baicalein 5,6,7-trimethyl ether, a flavonoid derivative may be a candidate for the therapeutic compound for ALD.
(4) We investigated the clinical, biochemical and molecular findings, and morphology of peroxisomes in Japanese patients with peroxisomal beta-oxidation enzymes deficiencies, including acyl-CoA oxidase (AOX) or D-3-hydroxyacyl-CoA dehydratase / D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein (D-BP).
(5) To clarify the molecular mechanism of a temperature-sensitive (TS) phenotype in PBD, we analyzed the protein 3D-structure of a SH3 domein of PEX13 protein, whose Ile326Thr mutation demonstrated a TS phenotype in peroxisomal biogenesis. These data indicated that the Ile326 should be a core residue for folding kinetics and the substitution of the Ile326 by threonine should directly alter the kinetic equilibrium, suggesting a marked increase of the unfolded molecules when the patient had a high fever.
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Research Products
(16 results)
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[Journal Article] Aberrant peroxisome morphology in peroxisomal beta-oxidation enzyme deficiencies2006
Author(s)
M Funato, N Shimozawa, T Nagase, Y Takemoto, Y Suzuki, Y Imamura, T Matsumoto, T Tsukamoto, T Kojidani, T Osumi, T Fukao, N Kondo
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Journal Title
Brain ＆ Development 28 (5)
Pages: 287-292
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Baicalein 5,6,7-trimethyl ether, a flavonoid derivative, stimulates fatty acid beta-oxidation in skin fibroblasts of X-linked adrenoleukodystrophy2005
Author(s)
Morita M, Takahashi I, Kanai M, Okafuji F, Iwashima M, Hayashi T, Watanabe S, Hamazaki T, Shimozawa N, Suzuki Y, Furuya H, Yamada T, Imanaka T
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Journal Title
FEBS Lett. 579(2)
Pages: 409-14
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Molecular Mechanism of a Temperature-Sensitive Phenotype in Peroxisomal Biogenesis Disorder2005
Author(s)
K Hashimoto, Z Kato, T Nagase, N Shimozawa, K Kuwata, K Omoya, A Li, E Matsukuma, Y Yamamoto, H Ohnishi, H Tochio, M Shirakawa, Y Suzuki, R JA Wanders, N Kondo
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Journal Title
Pediatr Res 58(2)
Pages: 263-9
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Natural history of X-linked adrenoleukodystrophy in Japan2005
Author(s)
Y Suzuki, Y Takemoto, N Shimozawa, T Imanaka, S Kato, H Furuya, M Kaga, K Kato, N Hashimoto, 0 Onodera, S Tsuji
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Journal Title
Brain ＆ Development 27(5)
Pages: 353-357
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Role of Pexl9p in the targeting og PMP70 to peroxisome2005
Author(s)
Kashiwayama Y, Asahina K, Shibata H, Morita M, Muntau AC, Roscher AA, Wanders RJA, Shimozawa N, Sakaguchi M, Kato H, Imanaka T
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Journal Title
Biochim Biophys Acta 1746
Pages: 116-128
Description
「研究成果報告書概要(欧文)」より
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