Abnormal tau-containing filaments in neurodegenerative diseases
Abnormal tau-containing filaments in neurodegenerative diseases
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DOI：
10.1006/jsbi.2000.4270
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发表时间：
2000-06-01
影响因子：
3
通讯作者：
Goedert, M
中科院分区：
文献类型：
--
作者：
Crowther, RA;Goedert, M
众所周知，阿尔茨海默病的神经纤维病理由微管相关蛋白tau组成的所谓的成对螺旋和直丝组成。在阿尔茨海默病中观察到的痴呆程度与神经纤维病理程度的相关性比与Aβ淀粉样沉积的相关性更好，Aβ淀粉样沉积是阿尔茨海默病中定义病理性纤维沉积的另一个特征。然而，还没有阿尔茨海默病家族病例与tau蛋白基因座有关。最近，一组与17号染色体相关的帕金森症患者被证明是由tau基因突变引起的。一些是错义突变，导致tau蛋白发生变化，而另一些则影响前-mRNA的剪接，并改变不同tau亚型之间的平衡。组织学上，这些疾病的特征都是各种丝状tau蛋白沉积，大多完全没有Aβ沉积。根据tau突变的性质，异常tau细丝表现出不同的形态。这些疾病表明tau突变可能是遗传性痴呆疾病的主要原因，并可能为数量更多的散发性阿尔茨海默病病例的病理过程提供一些线索。(C)2000年学术出版社。
It has been known for some time that the neurofibrillary pathology in Alzheimer's disease consists of so-called paired helical and straight filaments made up of the microtubule-associated protein tau. The degree of dementia observed in the disease correlates better with the extent of neurofibrillary pathology than with the A beta amyloid deposits, the other characteristic defining pathological fibrous deposit in Alzheimer's disease. However, no familial cases of Alzheimer's disease have been genetically linked to the tau protein locus. Recently a group of frontotemporal dementias with parkinsonism linked to chromosome 17 has been shown to be caused by mutations in the tau gene. Some are missense mutations giving altered tau proteins, whereas others affect the splicing of the pre-mRNA and change the balance between different tau isoforms. Histologically these diseases are all characterised by various kinds of filamentous tau protein deposits, mostly in the complete absence of A beta deposits. The abnormal tau filaments show different morphologies, depending on the nature of the tau mutation. These diseases show that tau mutations can be a prime cause of inherited dementing illness and may throw some light on the pathological process in the much larger number of sporadic cases of Alzheimer's disease. (C) 2000 Academic Press.