Analysis of activated glial cells by glycome abnoumality in lysosomal didease
Project/Area Number |
19790236
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Single-year Grants |
Research Field |
Pathological medical chemistry
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Research Institution | The University of Tokushima |
Principal Investigator |
TSUJI Daisuke The University of Tokushima, 大学院・ヘルスバイオサイエンス研究部, 助教 (00423400)
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Project Period (FY) |
2007 – 2009
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Project Status |
Completed (Fiscal Year 2009)
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Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥600,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,200,000 (Direct Cost: ¥1,200,000)
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Keywords | 先天性代謝異常症 / 糖脂質 / グリア細胞 / アストロサイト / ミクログリア / リソソーム病 / 神経変性疾患 / リソソーム |
Research Abstract |
Sandhoff disease (SD) is a lysosomal β-hexosaminidase (Hex) deficiency involving excessive accumulation of undegraded substrates, including terminal GlcNAc-oligosaccharides and GM2 ganglioside, and progressive neurodegeneration. In this study, we isolated astrocytes and microglia from the neonatal brain of Sandhoff disease model mice, and demonstrated the abnormalities of SD-glial cells. We found remarkable differences in the cell proliferation of SD astrocyte (ASD) when compared to cells isolated from wild type mice, with a faster growth rate of ASD cells. In addition, we observed increased ERK phosphorylation in ASD cells, but Akt phosphorylation was decreased. These results indicated that the up-regulation of ERK phosphorylation and the increase in proliferation of ASD astrocytes were dependent upon GM2/GA2 accumulation. Furthermore, inhibitors for PKC and Akt reduced the production of MIP-α or by SD-Micoglia. These findings may represent a mechanism in linking activation of glial cells observed in Sandhoff disease.
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Report
(4 results)
Research Products
(51 results)
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[Journal Article] Binding parameters and thermodynamics of the interaction of imino sugars with a recombinant human acid a-glucosidase (alglucosidase alfa): insight into the complex formation mechanism.2008
Author(s)
Yoshimizu M, Tajima Y, Matsuzawa F, Aikawa S, Iwamoto K, Kobayashi T, Edmunds T, Fujishima K, Tsuji D, Itoh K, Ikekita M, Kawashima I, Sugawara K, Ohyanagi N, Suzuki T, Togawa T, Ohno K, Sakuraba H.
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Journal Title
Clin Chim Acta 391(1-2)
Pages: 68-73
Related Report
Peer Reviewed
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[Journal Article] Production of recombinant b-hexosaminidase A, a potential enzyme for replacement therapy for Tay-Sachs and Sandhoff diseases, in the methylotrophic yeast Ogataea minuta.2007
Author(s)
Akeboshi H, Chiba Y, Kasahara Y, Takashiha M, Takaoka Y, Ohsawa M, Tajima Y, Kawashima I, Tsuji D, Itoh K, Sakuraba H, Jigami Y.
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Journal Title
Appl Environ Microbiol 73(15)
Pages: 4805-4812
Related Report
Peer Reviewed
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[Presentation] GM2ガングリオシドーシスモデルマウスに対する組換えヒトβ-ヘキソサミニダーゼの脳内補充効果2008
Author(s)
辻大輔, 安岡寛子, 松岡和彦, 宮崎絵梨, 廣瀬由記子, 明星裕美, 笠原由子, 千葉靖典, 地神芳文, 二木史朗, 櫻庭均, 伊藤孝司
Organizer
第50回日本脂質生化学会
Year and Date
2008-06-05
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