Nacharaju P, Lewis J, Easson C, Yen S, Hackett J, Hutton M, Yen S H
Department of Pharmacology, Mayo Clinic Jacksonville, FL 32224, USA.
FEBS Lett. 1999 Mar 26;447(2-3):195-9. doi: 10.1016/s0014-5793(99)00294-x.
Tau is the major component of the neurofibrillar tangles that are a pathological hallmark of Alzheimers' disease. The identification of missense and splicing mutations in tau associated with the inherited frontotemporal dementia and Parkinsonism linked to chromosome 17 demonstrated that tau dysfunction can cause neurodegeneration. However, the mechanism by which tau dysfunction leads to neurodegeneration remains uncertain. Here, we present evidence that frontotemporal dementia and Parkinsonism linked to chromosome 17 missense mutations, P301L, V337M and R406W, cause an accelerated aggregation of tau into filaments. These results suggest one mechanism by which these mutations can cause neurodegeneration and frontotemporal dementia and Parkinsonism linked to chromosome 17.
Tau蛋白是神经原纤维缠结的主要成分，而神经原纤维缠结是阿尔茨海默病的病理标志。在与17号染色体连锁的遗传性额颞叶痴呆和帕金森综合征相关的tau蛋白中发现错义突变和剪接突变，表明tau蛋白功能障碍可导致神经退行性变。然而，tau蛋白功能障碍导致神经退行性变的机制仍不确定。在此，我们提供证据表明，与17号染色体连锁的额颞叶痴呆和帕金森综合征错义突变P301L、V337M和R406W会导致tau蛋白加速聚集成细丝。这些结果提示了这些突变可导致神经退行性变以及与17号染色体连锁的额颞叶痴呆和帕金森综合征的一种机制。
