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An Additive-Free Model for Tau Self-Assembly

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Protein Aggregation

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2551))

Abstract

Tau is a natively unfolded protein that contributes to the stability of microtubules. Under pathological conditions such as Alzheimer’s disease (AD), tau protein misfolds and self-assembles to form paired helical filaments (PHFs) and straight filaments (SFs). Full-length tau protein assembles poorly and its self-assembly is enhanced with polyanions such as heparin and RNA in vitro, but a role for heparin or other polyanions in vivo remains unclear. Recently, a truncated form of tau (297–391) has been shown to self-assemble in the absence of additives which provides an alternative in vitro PHF model system. Here we describe methods to prepare in vitro PHFs and SFs from tau (297–391) named dGAE. We also discuss the range of biophysical/biochemical techniques used to monitor tau filament assembly and structure.

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Author information

Authors and Affiliations

  1. Chemistry Department, College of Science, Mustansiriyah University, Baghdad, Iraq

    Youssra K. Al-Hilaly

  2. Sussex Neuroscience, School of Life Sciences, University of Sussex, Sussex, UK

    Youssra K. Al-Hilaly, Karen E. Marshall, Luca Biasetti, Kurtis Mengham & Louise C. Serpell

  3. School of Biosciences, University of Kent, Canterbury, UK

    Liisa Lutter & Wei-Feng Xue

  4. Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK

    Charles R. Harrington & Claude M. Wischik

  5. TauRx Therapeutics Ltd., Aberdeen, UK

    Charles R. Harrington & Claude M. Wischik

  6. Institute of Genomics and Proteomics, University of California, Los Angeles, CA, USA

    Liisa Lutter

Authors
  1. Youssra K. Al-Hilaly
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  2. Karen E. Marshall
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  3. Liisa Lutter
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  4. Luca Biasetti
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  5. Kurtis Mengham
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  6. Charles R. Harrington
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  7. Wei-Feng Xue
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  8. Claude M. Wischik
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  9. Louise C. Serpell
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Corresponding author

Correspondence to Youssra K. Al-Hilaly .

Editor information

Editors and Affiliations

  1. Cambridge, MA, USA

    Andrzej Stanisław Cieplak

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Al-Hilaly, Y.K. et al. (2023). An Additive-Free Model for Tau Self-Assembly. In: Cieplak, A.S. (eds) Protein Aggregation. Methods in Molecular Biology, vol 2551. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2597-2_12

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  • DOI: https://doi.org/10.1007/978-1-0716-2597-2_12

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2596-5

  • Online ISBN: 978-1-0716-2597-2

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