Pathogenesis of the Tauopathies
Pathogenesis of the Tauopathies
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DOI：
10.1007/s12031-011-9593-4
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发表时间：
2011-11-01
影响因子：
3.1
通讯作者：
Spillantini, Maria Grazia
中科院分区：
文献类型：
--
作者：
Goedert, Michel;Spillantini, Maria Grazia
微管相关蛋白tau是人类神经退行性疾病中最常见的错误折叠蛋白，在那里它变得过度磷酸化和丝状。tau基因MAPT的突变导致大约5%的额颞叶痴呆病例。他们经常伴随着帕金森症。MAPT突变的存在已经确定tau蛋白的功能障碍足以引起神经变性和痴呆。然而，大多数tau蛋白病不是以显性方式遗传的。疾病之间的过度磷酸化位点是相似的，但细丝形态和tau亚型组成不同。这与多个tau构象异构体的存在是一致的，最近的研究结果为这一概念提供了实验支持。
Microtubule-associated protein tau is the most commonly misfolded protein in human neurodegenerative diseases, where it becomes hyperphosphorylated and filamentous. Mutations in MAPT, the tau gene, cause approximately 5% of cases of frontotemporal dementia. They are frequently accompanied by parkinsonism. The existence of MAPT mutations has established that dysfunction of tau protein is sufficient to cause neurodegeneration and dementia. However, most tauopathies are not inherited in a dominant manner. The hyperphosphorylated sites are similar between diseases, but filament morphologies and tau isoform compositions vary. This is consistent with the existence of multiple tau conformers and recent findings have provided experimental support for this concept.