Stable tubule only polypeptides (STOP) proteins co-aggregate with spheroid neurofilaments in amyotrophic lateral sclerosis
Stable tubule only polypeptides (STOP) proteins co-aggregate with spheroid neurofilaments in amyotrophic lateral sclerosis
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DOI：
10.1093/jnen/62.12.1211
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发表时间：
2003-12-01
影响因子：
3.2
通讯作者：
Eyer, J
中科院分区：
文献类型：
--
作者：
Letournel, F;Bocquet, A;Eyer, J
肌萎缩侧索硬化症(ALS)的一个主要细胞病理学特征是存在含有异常堆积的神经丝的轴突球体。它们的形成机制，它们对疾病的贡献，以及其他共聚集成分的可能性仍然是个谜。在这里，我们分析了这些损伤的组成，特别是稳定仅有小管的多肽(STOP)，这是一种负责微管冷稳定的蛋白质。在正常人脑和脊髓中，停止蛋白在神经元的胞浆和神经突起之间分布均匀。然而，所有存在于患者组织中的富含神经丝的球体都被3种不同的抗STOP抗体强烈标记。此外，当从脊髓和脑中分离神经细丝和微管时，Stop蛋白与神经细丝系统地共纯化。经SDS-PAGE分析，病理标本中STOP蛋白的迁移图谱未见改变。其他微管蛋白，如微管蛋白或动蛋白，不连续地存在于球体中，这表明微管失稳过程可能参与了ALS的发病机制。这些结果表明，神经丝和终止蛋白的选择性共聚集是球体的一种新的细胞病理学标记。
A major cytopathological hallmark of amyotrophic lateral sclerosis (ALS) is the presence of axonal spheroids containing abnormally accumulated neurofilaments. The mechanism of their formation, their contribution to the disease, and the possibility of other co-aggregated components are still enigmatic. Here we analyze the composition of such lesions with special reference to stable tubule only polypeptide (STOP), a protein responsible for microtubule cold stabilization. In normal human brain and spinal cord, the distribution of STOP proteins is uniform between the cytoplasm and neurites of neurons. However, all the neurofilament-rich spheroids present in the tissues of affected patients are intensely labeled with 3 different anti-STOP antibodies. Moreover, when neurofilaments and microtubules are isolated from spinal cord and brain, STOP proteins are systematically co-purified with neurofilaments. By SDS-PAGE analysis, no alteration of the migration profile of STOP proteins is observed in pathological samples. Other microtubular proteins, like tubulin or kinesin, are inconstantly present in spheroids, suggesting that a microtubule destabilizing process may be involved in the pathogenesis of ALS. These results indicate that the selective co-aggregation of neurofilament and STOP proteins represent a new cytopathological marker for spheroids.