The cause of neuropathochemistry of inherited Neurodegeneration

遗传性神经退行性疾病的神经学发现的原因尚不清楚。在这项研究中，我们试图阐明神经功能障碍的可能原因，特别是在高谢病中。高谢病的特征是由于溶酶体葡萄糖脑苷酶缺乏导致网状内皮细胞中葡萄糖脑苷的积聚。在高谢病患者的中枢神经组织中，糖脑苷的积聚很少。葡萄糖脑苷蓄积程度的差异似乎是细胞类型特有的现象。因此，我们使用不同的肿瘤细胞，如人少突胶质瘤细胞，人神经母细胞瘤细胞，验证了这些发现，康杜丽醇-B-环氧化物(CBE)是一种有效的溶酶体β-葡萄糖苷酶抑制剂。在培养的人少突胶质细胞瘤细胞中加入CBE，每瓶小于100ug/ml时，葡萄糖脑苷显著积累。同时，给予相同浓度的CBE可完全抑制酶活性。形态图片显示猪细胞膜胞质异常，而人神经母细胞瘤细胞膜胞质异常。这些数据表明，高谢病的形态特征因细胞而异。

The cause of neurological findings in inherited neurodegernerative disorders is unknown. In this studies, we attempt to elucidate the possible cause of neurological disorder, particularly in Gaucher disease.Gaucher disease is characterized by the accumulation of glucocerebroside in reticuloendotherial cells caused by a deficiency of lysosomal glucocerebrosidase. In central nervous tissues with Gaucher disease, there is few accumulation of glucocerebroside. The difference of the degree of accumulation of glucocerebroside seems to be cell type specific phenomenon. Therefore, we tested these finding using different tumor cells such as human oligodendroglioma cells, human neuroblastoma cells, Conduritol-B-epoxide (CBE) is a potent inhibitor for lysosomal betaglucosidase. Administration of CBE,less than 100ug/ml per bottle into cultured human oligodendroglioma cells produced significant accumulation of glucocerebroside. Simultaneously, enzyme activity was completely inhibited by administration of CBE at the same concentration. Morphological pictures shows abnormal membranous cytoplasmic body in HOG cells, whereas in human neuroblastoma cells. These data suggest the morphological picture in Gaucher disease is different from cells to cells.