A novel tau mutation in exon 9 (1260V) causes a four-repeat tauopathy
A novel tau mutation in exon 9 (1260V) causes a four-repeat tauopathy
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DOI：
10.1016/s0014-4886(03)00393-5
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发表时间：
2003-11-01
影响因子：
5.3
通讯作者：
Hutton, M
中科院分区：
文献类型：
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作者：
Grover, A;England, E;Hutton, M
tau蛋白9外显子I260V的新突变与一种临床综合征相关，该综合征与具有广泛tau病理学的额颞叶痴呆相一致；但未见神经原纤维缠结和匹克体。值得注意的是，从受影响的脑组织中提取的萨科齐不溶性tau几乎完全由四重复亚型组成。与这些发现一致的是，体外生化分析表明，I260V突变导致tau聚集选择性增加，而tau诱导的微管组装仅具有四重复亚型。该突变的病理和生化效应的对比表明，与其他外显子9突变不同的疾病机制，并证明了第一微管结合结构域在tau促进的微管组装和tau的致病性聚集中的关键作用。(C) 2003 Elsevier Inc.版权所有。
A novel mutation in exon 9 of tau, I260V, is associated with a clinical syndrome consistent with frontotemporal dementia with extensive tau pathology; however, neurofibrillary tangles and Pick bodies are absent. Significantly, Sarkosyl- insoluble tau extracted from affected brain tissue consisted almost exclusively of four-repeat isoforms. Consistent with these findings, in vitro biochemical assays demonstrated that the I260V mutation causes a selective increase in tau aggregation and a decrease in tau-induced microtubule assembly with four-repeat isoforms only. The contrasting pathology and biochemical effects of this mutation suggest a different disease mechanism from the other exon 9 mutations and demonstrates the critical role for the first microtubule-binding domain in tau-promoted microtubule assembly and the pathogenic aggregation of tau. (C) 2003 Elsevier Inc. All rights reserved.