The Pathogenesis of Demyelination in Krabbe's disease and it's therapy

克拉伯病脱髓鞘的发病机制及治疗

• 批准号: 63570456
• 负责人: TOKORO Toshiharu
• 金额: $ 1.28万
• 依托单位: The Jikei University School of Medicine, Department of Pediatrics
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570456/
• 关键词: Krabbe's disease; Psychosine; Twitcher mouse; Niemann-Pick mouse; Lysosomal disorder; 神経培養; E-64; (1)krabbe病; (2)サイコシン; (3)脱髄; (4)培養オリゴデンドロサイト; (5)Twitcherマウス

We investigated the pathogenesis of demyelination in Krabbe's disease using Twitcher mouse and the cholesterol metabolism in Niemann-Pick mouse model.1. Marked accumulation of psychosine was found in the Twitcher mouse Dorsal Root Ganglion. And psychosine played an important role for the demyelination in Floboid Cell Leukodystrophy.2. Psychosine inhibited the incorporation of H-galactose into cerebroside and sulfatide in cultured colgodendroglia. This results suggested that psycgosine participate in the demyelination in vitro.3. Psychosine treated cells showed destruction of cytoskeleton and suggested that psychosine influences mitochondrial function, possibly through the inhibition of oxidative phosphorylation.4. Liposomes prepared from p-aminophenyl-alpha-mannoside were sufficiently incorporated into the mouse brain across the blood brain barrier. It was suggested that glial cell recognize mannose molecude on the surface of the membrane.5. It was found that the exogenous cholesterol esterification was found in Niemann-Pick mouse fibroblasts. The impaired cholesterol esterification might be an important role for the pathogenesis of Niemann-Pick mouse model.

本研究采用Twitcher小鼠模型和Niemann-Pick小鼠模型研究Krabbe病脱髓鞘的发病机制和胆固醇代谢.在Twitcher小鼠背根神经节中发现了明显的精神病碱蓄积。结论：1.精神分裂素在梭形细胞脑白质营养不良的脱髓鞘过程中起重要作用. Psychosine可抑制H-半乳糖掺入培养的胶质细胞中的β-半乳糖苷和硫苷脂。提示Psycgosine参与了体外脱髓鞘过程.精神碱处理的细胞显示细胞骨架的破坏，表明精神碱影响线粒体功能，可能通过抑制氧化磷酸化.由对氨基苯基-α-甘露糖苷制备的脂质体穿过血脑屏障充分掺入小鼠脑中。提示胶质细胞识别膜表面的甘露糖分子.结果发现，在Niemann-Pick小鼠成纤维细胞中存在外源性胆固醇酯化。胆固醇酯化功能受损可能是Niemann-Pick小鼠模型发病机制中的一个重要环节。

项目成果

Hiroyuki Ida: "Biochemical Pathogenesis of Demyelination in Globoid Cell Leukodystrophy(Krabbe's disaese)" Acta.Ped.Jap.(1990)

Hiroyuki Ida：“球状细胞脑白质营养不良（克拉伯氏病）脱髓鞘的生化发病机制”Acta.Ped.Jap.（1990）

Hiroyuki Ida: "Neurotoxity of Psychosine in Neural Cell Cultures; The Pathogenesis and Mechanisms." Tohoku J. Exp. Med. 1990, in Press.

Hiroyuki Ida：“神经细胞培养物中 Psychosine 的神经毒性；发病机制和机制。”

P.G.Pentcher・;Comly M.;E・Tokoro T: FASBE. 40-45 (1988)

P.G.Pentcher・；Comly M.；E・Tokoro T：FASBE。

Fusayo Umezawa: "Liposomal tergeting of Mouse Brain as a Reconbination Marker." Biochemical Biophysical Reserch Communication. 153. 1038-1044 (1988)

Fusayo Umezawa：“小鼠大脑的脂质体靶向作为重组标记。”

Hiroyuki Ida: "Biochemical Pathogenesis of Demyelination in Globoid Cell Leukodystrophy(Krabbe's disease)" Acta.Ped.Jap.(1990)

Hiroyuki Ida：“球状细胞脑白质营养不良（克拉伯氏病）脱髓鞘的生化发病机制”Acta.Ped.Jap.（1990）