Immunochemical demonstration of tropomyosin in the neurofibrillary pathology of Alzheimer's disease.
Immunochemical demonstration of tropomyosin in the neurofibrillary pathology of Alzheimer's disease.
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发表时间：
1990
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通讯作者：
P. Galloway;P. Mulvihill;S. Siedlak;M. Mijares;M. Kawai;H. Padget;R. Kim;George Perry
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作者：
P. Galloway;P. Mulvihill;S. Siedlak;M. Mijares;M. Kawai;H. Padget;R. Kim;George Perry
阿尔茨海默病神经原纤维病理学（NFP）的研究重点不仅在于确定形成配对螺旋丝的成分，还在于确定它们是否是由影响单个蛋白质的异常过程引起的。因此，尽管这些研究引发了关于微管和神经丝成分各自贡献的争议，但基本上没有考虑其他细胞骨架系统是否也可能参与以及所合并成分的共同特征是什么。与这个问题特别相关的是我们的发现，针对骨骼或平滑肌原肌球蛋白（一种微丝成分）的几种抗血清能够强烈识别 NFP。这些抗体在对原肌球蛋白或配对螺旋丝片段进行亲和纯化后继续识别 NFP。我们表明，由于与先前鉴定的与神经丝和微管、tau 和 MAP2 或神经丝蛋白相关的 NFP 成分发生交叉反应，这些抗体不识别 NFP，因为抗血清在免疫印迹上不识别这些蛋白质或不可被蛋白质吸附。免疫反应的超微结构分析表明，原肌球蛋白相关表位成簇分布，而不是沿着成对的螺旋和直丝均匀分布。尽管分布表明原肌球蛋白是一种 NFP 相关蛋白，但去垢剂提取后，其通过成对的螺旋和直丝保留，表明它是与 NFP 丝特征强烈且特异性相关的组成部分。这些发现表明，NFP涉及三种主要神经元细胞骨架丝系统：微管、神经丝以及微丝，因此NFP可能是这些正常丝的重组的结果，这些正常丝相互作用构成细胞基质，并且可能在阿尔茨海默氏病的病理条件下继续这种相互作用，产生新的异常聚合物。
The focus of research on the neurofibrillary pathology (NFP) of Alzheimer disease has been not only to determine the component forming the paired helical filaments but also to determine whether they result from abnormal processes affecting a single protein. Therefore, although these studies have lead to controversy concerning the respective contribution of components of microtubules and neurofilaments, there has been essentially no consideration of whether other cytoskeletal systems might also be involved and of what are the common features for the incorporated components. Particularly relevant to this issue is our finding that several antisera raised to either skeletal or smooth muscle tropomyosin, a microfilament component, intensely recognize NFP. These antibodies continue to recognize NFP after affinity purification to tropomyosin or paired helical filament fractions. We show that the antibodies do not recognize NFP due to cross-reactivity with the previously identified NFP components related to neurofilaments and microtubules, tau, and MAP2, or neurofilament proteins because the antisera did not recognize these proteins on immunoblots or were not adsorbable by the proteins. Ultrastructural analysis of the immunoreaction showed that tropomyosin-related epitopes were clustered rather than uniformly distributed along paired helical and straight filaments. Although the distribution suggests that tropomyosin is an NFP-associated protein, its retention by paired helical and straight filaments after detergent extraction indicates that it is an integral component strongly and specifically associated with the filaments characteristic of NFP. These findings indicate that NFP involves the three primary neuronal cytoskeletal filament systems, microtubules, neurofilaments, as well as microfilaments, and therefore that NFP probably results from the reorganization of these normal filaments that interact to comprise the cytomatrix and may continue this interaction under the pathologic condition of Alzheimer's disease to generate novel, abnormal polymers.