The Morphogenesis and Biochemical Characteristics of Ceroid Isolated from Cases of Neuronal Ceroid-Lipofuscinosis
The Morphogenesis and Biochemical Characteristics of Ceroid Isolated from Cases of Neuronal Ceroid-Lipofuscinosis
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神经元蜡样质脂褐质沉着症病例分离蜡样质的形态发生和生化特征
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发表时间：
1972
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通讯作者：
W. Zeman
中科院分区：
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作者：
A. Siakotos;H. Goebel;V. Patel;I. Watanabe;W. Zeman
两组明显不同的疾病出现了一般归类为黑蒙性家族性白痴的条件。一种以脑鞘脂的严重异常谱为特征，例如GM1和GM2神经节苷脂。另一组是由正常的鞘脂谱，但与神经元积累的蜡样脂褐质型脂色素的患者。许多研究者已证明鞘脂增多症符合Hers（1965）关于溶酶体疾病的经典概念。这一观点已被不断的研究反复证实，这些研究表明特定水解酶的缺乏或减少，导致不能降解为代谢可利用物质的生化化合物的积累。溶酶体疾病的概念已导致许多研究人员寻找一个单一的积累脂质或缺乏水解酶独特的神经元蜡样脂褐质。由于许多溶酶体疾病通过阐明一种非生理性大量存在的特定脂质的化学性质而得到更好的理解，因此Donahue等人（1966）在该小组之前的声明，即“细胞质脂色素颗粒（来自Batten病患者的大脑）的化学分析对理解这种疾病几乎没有贡献”，显然是不明智的。虽然自发荧光脂色素缺乏化学特异性并由多种致病情况引起是正确的（Porta和Hartroft，1969），但Donahue等人（1966）未能认识到这些残留体的化学组成和超微结构中的某些重复模式可能表明特定的形成性发病机制的明显可能性。基于这一论点，我们开发了分离纯制剂中脂色素的方法，初步结果已经证明了这一概念的合理性。事实证明，以前持有的脂褐质和蜡样物质之间密切关系的概念必须被放弃，并被这些类别的脂色素是明显不同的实体的论点所取代，尽管两者都代表残留体并且都含有聚合物质（Siakotos等人，1970年）。
Two distinctly different groups of disorders have emerged from the conditions generically classified as amaurotic familial idiocies. One is characterized by grossly abnormal profiles for cerebral sphingolipids, for example the GM1 and GM2 gangliosides. The other group is composed of patients with normal sphingolipid profiles, but with neuronal accumulation of lipopigments of the ceroid-lipofuscin type. The sphingolipidoses have been shown by a number of investigators to meet the classic concept of Hers (1965) for lysosomal diseases. This view has been repeatedly reinforced by continuing studies which show the lack or reduction of specific hydrolases, resulting in the accumulation of biochemical compounds which cannot be degraded to metabolically utilizable substances. The concept of lysosomal diseases has led many investigators to search for a single accumulating lipid or a deficient hydrolytic enzyme unique to neuronal ceroid-lipofuscinoses. Since many of the lysosomal disorders became better understood by the elucidation of the chemical properties of a specific lipid, present in unphysiologically large quantities, the pronouncement by Donahue et al. (1966) before this group, that the “chemical analysis of cytoplasmic lipopigment granules (from the brains of patients with Batten’s disease) will contribute little towards an understanding of this disease” was decidedly unwise. Although it is correct, that autofluorescent lipopigments lack chemical specificity and result from a great variety of pathogenetic situations (Porta and Hartroft, 1969), Donahue et al. (1966) failed to recognize the distinct possibility, that certain repetitive patterns in the chemical composition and ultrastructure of these residual bodies may indicate a specific formative pathogenesis. On the strength of this argument, we developed methods to isolate lipopigments in pure preparations and the first results have proved already the soundness of this concept. As it turned out, the previously held concept of a close relationship between lipofuscin and ceroid had to be abandoned and replaced by the theses that these classes of lipopigment are distinctly different entities, albeit both represent residual bodies and both contain polymeric substances (Siakotos et al., 1970).