Accelerated filament formation from tau protein with specific FTDP‐17 missense mutations

FEBS Letters

Lewis, Jada¹  Hutton, Mike¹  Hackett, Jennifer¹  Nacharaju, Parimala¹  Yen, Samuel¹  Yen, Shu-Hui¹  Easson, Colin¹ 

[1]Departments of Pharmacology and Biochemistry and Molecular Biology, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA

关键词: Frontotemporal dementia and Parkinsonism linked to chromosome 17;    Neurodegeneration;    Tau polymerization;    Tau mutation;    Tauopathy;   

DOI  :  10.1016/S0014-5793(99)00294-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown