The prion protein in human neuromuscular diseases
The prion protein in human neuromuscular diseases
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DOI：
10.1002/path.1633
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发表时间：
2004-11-01
影响因子：
7.3
通讯作者：
Budka, H
中科院分区：
文献类型：
--
作者：
Kovács, GG;Kalev, O;Budka, H
影响神经系统的人类朊病毒疾病的基础是正常细胞朊病毒蛋白（PrPC）的疾病相关构象异构体（PrPSc）的积累。早期的研究表明PrPC在包涵体肌炎（IBM）、皮肤炎和多发性肌炎以及神经源性肌肉萎缩中表达增加。为了定义光谱和可靠性的PrPC免疫反应性，其表达进行了系统的研究，在一系列的病理特征的肌肉疾病，通过免疫组织化学，共聚焦激光显微镜，免疫金电子显微镜。在IBM中观察到抗PrPC免疫标记的镶边空泡，包括myolibrillary肌病，目标，再生和萎缩的纤维，单核细胞，除了在线粒体肌病中的粗糙的红色纤维，和非疾病对照中的局部肌纤维膜免疫染色。定量分析表明，在神经源性肌肉病变中，抗PrPC染色检测到比抗波形蛋白或抗NCAM显著更广谱的纤维。在营养不良的肌肉，PrPC的表达主要限于再生纤维。在IBM中，PrPC表达不局限于镶边空泡或空泡化纤维，只有一小部分（7.1%）镶边空泡PrPC阳性。超微结构，PrPC中观察到的淋巴细胞的细胞质中，在肌原纤维网络的目标，并在镶边空泡。了解PrPC表达改变的疾病情况对于潜在增加神经性（PrP-CPrPSc）转化的机会非常重要。此外，我们的观察表明，PrPC可能有一个一般的压力反应的影响，在各种神经肌肉疾病。版权所有（C）2004大不列颠和爱尔兰病理学会。出版社：John Wiley Sons，Ltd
The basis of human prion diseases affecting the nervous system is accumulation of a disease-associated conformer (PrPSc) of the normal cellular prion protein (PrPC). Earlier studies demonstrated increased expression of PrPC in inclusion body myositis (IBM), dermato-, and polymyositis, as well as neurogenic muscle atrophy. To define the spectrum and reliability of PrPC immunoreactivity, its expression was examined systematically in a series of pathologically characterized muscular disorders by means of immunohistochemistry, confocal laser microscopy, and immunogold electron microscopy. Anti-PrPC immunolabelling of rimmed vacuoles was observed in IBM, inclusions of myolibrillary myopathy, targets, regenerating, and atrophic fibres, mononuclear cells, in addition to ragged red fibres in mitochondrial myopathies, and focal sarcolemmal immunostaining in non-diseased controls. Quantitative analysis demonstrated that, in neurogenic muscle lesions, anti-PrPC staining detects a significantly broader spectrum of fibres than anti-vimentin or anti-NCAM. In dystrophic muscle, PrPC expression was mainly restricted to regenerating fibres. In IBM, PrPC expression was not confined to rimmed vacuoles or vacuolated fibres and only a small percentage (7.1%) of rimmed vacuoles were PrPC positive. Ultrastructurally, PrPC was observed in the cytoplasm of lymphocytes, in the myofibrillar network of targets, and in rimmed vacuoles. Knowledge of disease circumstances with altered expression of PrPC is important in the setting of a potentially increased chance for extraneural (PrP-CPrPSc) conversion. In addition, our observations suggest that PrPC may have a general stress-response effect in various neuromuscular disorders. Copyright (C) 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley Sons, Ltd.