神经节苷脂促进细胞内β-淀粉样蛋白生成的机制  

Mechanism by which ganglioside GM1 promotes the production of intracellular amyloid β-protein

作　　者：王雪[1] 何其华[2] 阮燕[1] 张岱[1] 

机构地区：[1]北京大学精神卫生研究所,北京100083 [2]北京大学基础医学院,北京100083

出　　处：《中国病理生理杂志》2003年第1期6-9,I002,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.39870 2 76 ;38940 0 1 0 ) ;国家重点基础研究发展规划项目(No.G1 9990 640 0 7)

摘　　要：目的 :本研究着重分析和探讨神经节苷脂 (GM1 )促进细胞内 β -淀粉样蛋白 (Aβ)生成、聚积的作用机制。方法 :采用人类APP6 95cDNA转染人成神经细胞瘤细胞株 (HY -SY5Y)为模型 ,应用IP -Western印迹法检测不同浓度GM1处理后 ,细胞内Aβ生成量的变化 ;应用激光共聚焦扫描显微术 (LSCM)确定GM1作用的具体亚细胞分布部位。结果 :实验表明 ,细胞内Aβ含量随GM1浓度的增加而明显递增 (P <0 0 1 ,n =6) ;内 /外源性GM1分别与细胞内Aβ4 2 协同分布在内质网内。结论 :GM1与Aβ4 2 在亚细胞器内的协同分布对于Aβ4 2 在细胞内聚积。AIM: This research emphasizes the effect of ganglioside GM1 on generation of the intracellular amyloid β-protein(Aβ) and investigates where and how GM1 promoted the production of intracellular Aβ, particularly the more highly amyloidogenic Aβ 42 which is basis of senile plaque.METHODS: Human neuroblastoma cells transfected with human amyloid precursor protein (APP) cDNA were used to analyze the effect of the various concentrations of GM1 on the level of intracellular total Aβ by IP-Western blot. Subcellular compartment localized and colocalized with intracellular Aβ 42 was determined by double or triple immunofluorescence labeling.RESULTS: The intracellular total Aβ was promoted by GM1, and the levels of intracellular Aβ were correlated to the concentrations of GM1 in a dose-dependent fashion ( P<0 01, n=6 ); GM1 was shown to overlap with Aβ 42 in the same subcellular compartment (ER) by Confocal. CONCLUSIONS: These results implicated that the co-localization of GM1 with intracellular Aβ 42 in the same site was very significant to the deposition and toxicity of Aβ 42 . This provides important data and clues for the mechanism of Alzheimer's Disease (AD) pathogenesis and a molecular link between gangliosides and formation of senile plaque.

关 键 词：阿尔茨海默病 神经节苷脂类 淀粉样Β蛋白 

分 类 号：R749.16[医药卫生—神经病学与精神病学]