Polyglutamine-containing proteins in schizophrenia
Polyglutamine-containing proteins in schizophrenia
复制标题
DOI：
10.1038/sj.mp.4000480
复制
发表时间：
1999-01-01
影响因子：
11
通讯作者：
Rouleau, G
中科院分区：
文献类型：
--
作者：
Joober, R;Benkelfat, C;Rouleau, G
据报道，精神分裂症中存在遗传预期，表现为连续几代疾病的严重程度增加和发病年龄较早。几种神经退行性疾病中预期的分子基础是编码CAG重复扩增的不稳定。最近，研究表明，与正常对照相比，精神分裂症患者中增加的CAG/CTG重复序列过多。总之，这些观察结果表明，不稳定的 CAG 重复序列可能在精神分裂症的病因学中发挥作用。本研究的目的是测试精神分裂症患者的淋巴母细胞系提取的总蛋白提取物中是否存在由 CAG 重复序列编码的聚谷氨酰胺扩增束，通过以下方法分离来自精神分裂症患者 (n = 59) 和正常对照 (n = 73) 的蛋白： SDS-聚丙烯酰胺凝胶电泳，湿印到硝酸纤维素膜上，并用识别扩展的聚谷氨酰胺阵列的单克隆抗体（mab 1C2）进行探测，在两名不相关的精神分裂症患者和其中一名患者的兄弟姐妹中鉴定出与分子量约为 50 kDa 的蛋白质相对应的三个异常条带。正常对照中没有一个检测出该异常条带呈阳性。这些结果表明，扩展的含聚谷氨酰胺蛋白质虽然罕见，但可能在精神分裂症的发病机制中发挥作用。
Genetic anticipation, manifested by increased severity and earlier age-at-onset of the disease over successive generations, is reported in schizophrenia, The molecular basis of anticipation in several neurodegenerative diseases is unstable coding CAG repeat expansions, Anticipation was reported in schizophrenia, Recently, studies suggested that enlarged CAG/CTG repeats are over represented in schizophrenic patients compared to normal controls. Together, these observations suggest that unstable CAG repeats may play a role in the etiology of schizophrenia, The purpose of this study is to test for the presence of polyglutamine-expanded tracts, encoded by CAG repeats, in total protein extracts derived from lymphoblastoid cell lines of schizophrenic patients, Proteins from schizophrenic patients (n = 59) and normal controls (n = 73) were separated by means of SDS-polyacrylamide gel electrophoresis, wet blotted onto nitrocellulose membrane and probed with a monoclonal antibody (mab 1C2) recognizing expanded polyglutamine arrays, Three abnormal bands corresponding to protein(s) of molecular weight of approximately 50 kDa were identified in two unrelated schizophrenic patients and in a sibling of one of these patients. None of the normal controls tested positive for this abnormal band, These results suggest that expanded polyglutamine-containing proteins, though rare, may play a role in the pathogenesis of schizophrenia.