Genetic analysis of the polymorphic carbohydrate structures of gengliasides for nerve regeration and a novel therpeutic approach

用于神经再生的更年期碳水化合物多态性结构的遗传分析和新的治疗方法

• 批准号: 12671949
• 负责人: MIZUNO Akio
• 金额: $ 1.79万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671949/
• 关键词: Ganglioside; Regeneration; Hypoglossal Nerve; Knockout mouse; b-series; 神経軸索再生; ガングリオシド; 人工神経; regeneration; Tg mouse; Knochout mouse; rat; 複合酸性糖脂質; 神経再生; 遺伝子解明; 臨床応用

The polymorphic carbohydrate structures of gangliosides play regulatory roles. In particular, b-series gangliosides, all of which contain alpha-2,8 sialic acids, have been considered to be critical in various biological events such as adhesion, toxin binding, neurite extension, cell growth, and apoptotis. To clarify the physiological functions of b-series gangliosides in viva, we have established a gene knockout mouse of GDS syntliase. Arthough all 'o-series structures were detieted in he mutant mice, they showed an almost complete nervous tissue morphology with no apparent abnormal behavior. Moreover, no differences in Fas-mediated apoptotic reaction of lymphocytes between wild type and the mutant mice were detected. However, the mutant mice exhibited clearly 'reduced regeneration of axotomized hypoglossal nerves compared with the wild type, suggesting that b-series gangliosides are more important in the repair rather than the differentiation of the nervous system and apoptotic process induced via Fas.

神经节苷脂的多态碳水化合物结构起着调节作用。特别是B系列神经节苷脂，它们都含有α-2，8-唾液酸，被认为在各种生物事件中起关键作用，如黏附、毒素结合、轴突延伸、细胞生长和细胞凋亡。为了阐明b系列神经节苷脂在体内的生理功能，我们建立了GDS合成酶基因敲除小鼠。虽然突变型小鼠的O-系列结构全部消失，但它们的神经组织形态几乎是完整的，没有明显的异常行为。此外，野生型和突变型小鼠在Fas介导的淋巴细胞凋亡反应方面也没有差异。但突变型小鼠舌下神经切断后再生明显减少，这表明b-系列神经节苷脂在修复过程中比在Fas诱导的神经系统分化和细胞凋亡过程中更重要。

项目成果

Okada M, Itoh M, Haraguchi, M., Okajima, T., Inoue, H., Furukawa, K.: "b-series ganglioside locking mice and showed no changes in the neurogenesis and sensitivity to Fas-mediated apoptosis but exhibited regeneration"J Bio Chem. 277. 1633-1636 (2002)

Okada M、Itoh M、Haraguchi, M.、Okajima, T.、Inoue, H.、Furukawa, K.：“b 系列神经节苷脂锁定小鼠的神经发生和对 Fas 介导的细胞凋亡的敏感性没有变化，但表现出再生

Itoh M, Izumi S., Uemura M., Baba N., Suyama K., Kuga Y., Mizuno A: "Prevention of death of axotomized hypoglossal neurons and promotion of regeneration by chitin grafting"Cellular and Molecular Neurobiology. 20・5. 529-540 (2000)

Itoh M、Izumi S.、Uemura M.、Baba N.、Suyama K.、Kuga Y.、Mizuno A：“通过几丁质移植预防轴突舌下神经元的死亡和促进再生”细胞和分子神经生物学20・5。 .529-540 (2000)

Itoh M., Fukumoto S., Iwamoto T., Mizuno A., Rokutanda A., Ishida H.-K., Kiso M., Furukawa k.: "Specificity Of carbohydrate structures of gangliosides in the activity to regenerate the rat axoto.mized hypoglossal nerve."Glycobiology. 11. 125-130 (2001)

Itoh M.、Fukumoto S.、Iwamoto T.、Mizuno A.、Rokutanda A.、Ishida H.-K.、Kiso M.、Furukawa k.：“神经节苷脂碳水化合物结构在大鼠轴突再生活性中的特异性

M.Itoh: "Specificity of Carbohydrate stmctures of gongliosides in the activity to regenerate the rat axotomiged hypoglossal nerne"Glycobiology. 11・2. 125-130 (2001)

M.Itoh：“神经节苷脂的碳水化合物结构在再生大鼠轴突舌下神经活性中的特异性”糖生物学11・2（2001）。

Itoh, M., Fukumoto, S., Iwamoto, T., Mizuno, A., Rokutanda, A., Furukawa, K.: "Specificity of carbohydrate structures of gangliosides in the activity to regenerate the rat axotomized hypoglossal nerve"Glycobiology. 11. 125-130 (2001)

Itoh, M.、Fukumoto, S.、Iwamoto, T.、Mizuno, A.、Rokutanda, A.、Furukawa, K.：“神经节苷脂碳水化合物结构在大鼠轴突舌下神经再生活性中的特异性”糖生物学。