THE IRON-BINDING PROTEIN LACTOTRANSFERRIN IS PRESENT IN PATHOLOGICAL LESIONS IN A VARIETY OF NEURODEGENERATIVE DISORDERS - A COMPARATIVE IMMUNOHISTOCHEMICAL ANALYSIS
THE IRON-BINDING PROTEIN LACTOTRANSFERRIN IS PRESENT IN PATHOLOGICAL LESIONS IN A VARIETY OF NEURODEGENERATIVE DISORDERS - A COMPARATIVE IMMUNOHISTOCHEMICAL ANALYSIS
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DOI：
10.1016/0006-8993(94)90202-x
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发表时间：
1994-07-04
期刊：
影响因子：
2.9
通讯作者：
HOF, PR
中科院分区：
文献类型：
--
作者：
LEVEUGLE, B;SPIK, G;HOF, PR
乳转铁蛋白是一种糖蛋白，专门结合和运输铁。这种蛋白质还被认为可以运输铝等其他金属。多条证据表明，铁和铝与许多痴呆疾病的发病机制有关。在这种情况下，分析受神经退行性疾病影响的患者大脑中的铁结合蛋白分布是特别有趣的。本研究用免疫组织化学方法分析了阿尔茨海默病、唐氏综合征、关岛肌萎缩侧索硬化症/帕金森病-痴呆复合体、散发性肌萎缩侧索硬化症或匹克病患者大脑皮质中乳铁蛋白的分布。结果表明，乳转铁蛋白在所研究的不同病理条件下的特征性皮损中积累。例如，在阿尔茨海默病和关岛病例中，神经原纤维缠结的一个亚群在海马结构和下颞叶皮质被强烈标记。老年斑和Pick小体也被一致地标记。这些染色模式与微管相关蛋白tau和淀粉样βA4蛋白抗体的染色模式相似，尽管乳转铁蛋白阳性的神经纤维缠结通常比tau蛋白阳性的少。在正常衰老的锥体神经元亚群中观察到乳转铁蛋白抗体的神经元胞浆染色，在阿尔茨海默病、关马尼亚病例、匹克病，尤其是唐氏综合征中更为明显。乳转铁蛋白还与对照组、阿尔茨海默病、唐氏综合症、瓜马尼亚人和匹克病患者的初级运动皮质中的Betz细胞和其他运动神经元密切相关。在肌萎缩侧索硬化症患者中，这些乳转铁蛋白免疫反应阳性的运动神经元受到严重影响。在这些神经退行性疾病中，受影响的神经元可能吸收或合成乳转铁蛋白的速率异常升高。乳转铁蛋白的过度蓄积以及转运的铁和铝可能会导致细胞毒性作用，导致细胞内病变的形成和神经元死亡。
Lactotransferrin is a glycoprotein that specifically binds and transports iron. This protein is also believed to transport other metals such as aluminum. Several lines of evidence indicate that iron and aluminum are involved in the pathogenesis of many dementing diseases. In this context, the analysis of the iron-binding protein distribution in the brains of patients affected by neurodegenerative disorders is of particular interest. In the present study, the distribution of lactotransferrin was analyzed by immunohistochemistry in the cerebral cortex from patients presenting with Alzheimer's disease, Down syndrome, amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam, sporadic amyotrophic lateral sclerosis, or Pick's disease. The results show that lactotransferrin accumulates in the characteristic lesions of the different pathologic conditions investigated. For instance, in Alzheimer's disease and Guamanian cases, a subpopulation of neurofibrillary tangles was intensely labeled in the hippocampal formation and inferior temporal cortex. Senile plaques and Pick bodies were also consistently labeled. These staining patterns were comparable to those obtained with antibodies to the microtubule-associated protein tau and the amyloid beta A4 protein, although generally fewer neurofibrillary tangles were positive for lactotransferrin than for tau protein. Neuronal cytoplasmic staining with lactotransferrin antibodies, was observed in a subpopulation of pyramidal neurons in normal aging, and was more pronounced in Alzheimer's disease, Guamanian cases, Pick's disease, and particularly in Down syndrome. Lactotransferrin was also strongly associated with Betz cells and other motoneurons in the primary motor cortex of control, Alzheimer's disease, Down syndrome, Guamanian and Pick's disease cases. These same lactotransferrin-immunoreactive motoneurons were severely affected in the cases with amyotrophic lateral sclerosis. It is possible that in these neurodegenerative disorders affected neurons either take up or synthesize lactotransferrin to an abnormally elevated rate. An excessive accumulation of lactotransferrin, as well as transported iron and aluminum, may lead to a cytotoxic effect resulting in the formation of intracellular lesions and neuronal death.