Tau (297-391) forms filaments that structurally mimic the core of paired helical filaments in Alzheimer’s disease brain

FEBS Letters

article

Youssra K. Al-Hilaly¹  Bronwen E. Foster¹  Luca Biasetti¹  Liisa Lutter³  Saskia J. Pollack¹  Janet E. Rickard⁴  John M. D. Storey⁵  Charles R. Harrington⁴  Wei-Feng Xue³  Claude M. Wischik⁴  Louise C. Serpell¹ 

[1] Dementia Research Group, School of Life Sciences, University of Sussex;Chemistry Department, College of Science, Mustansiriyah University;School of Biosciences, University of Kent;Institute of Medical Sciences, University of Aberdeen;Department of Chemistry, University of Aberdeen;TauRx Therapeutics Ltd.

关键词: Alzheimer’s disease;    neurofibrillary tangles;    paired helical filaments;    tau;   

DOI  :  10.1002/1873-3468.13675

来源: John Wiley & Sons Ltd.

【 摘 要 】

The constituent paired helical filaments (PHFs) in neurofibrillary tangles are insoluble intracellular deposits central to the development of Alzheimer’s disease (AD) and other tauopathies. Full-length tau requires the addition of anionic cofactors such as heparin to enhance assembly. We have shown that a fragment from the proteolytically stable core of the PHF, tau 297-391 known as ‘dGAE’, spontaneously forms cross-b-containing PHFs and straight filaments under physiological conditions. Here, we have analysed and compared the structures of the filaments formed by dGAE in vitro with those deposited in the brains of individuals diagnosed with AD. We show that dGAE forms PHFs that share a macromolecular structure similar to those found in brain tissue. Thus, dGAEs may serve as a model system for studying core domain assembly and for screening for inhibitors of tau aggregation.

【 授权许可】

Unknown