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bioRxiv · 10.1101/2020.12.07.414532

Oxidative stress conditions result in trapping of PHF-core tau (297-391) intermediates.

Maina, M. B.·Al-Hilaly, Y.·Burra, G. B.·Rickard, J.·Harrington, C.·Wischik, C.·Serpell, L.
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Abstract

The self-assembly of tau into paired helical filaments (PHF) in neurofibrillary tangles (NFTs) is a significant event in Alzheimers disease (AD) pathogenesis. Oxidative stress, which accompanies AD, induces multiple post-translational modifications in proteins including the formation of dityrosine (DiY) cross-links, previously observed for A{beta}. Here, metal catalysed- and ultra-violet oxidation were used to study the influence of DiY cross-linking on the self-assembly of the PHF-core tau fragment. We report that DiY cross-linking facilitates tau assembly into tau oligomers and prevents their elongation into filaments. The DiY cross-linked tau oligomers were not toxic to cells. Our findings suggest that DiY cross-linking of pre-assembled tau, promotes the formation of soluble tau oligomers that show no acute toxicity.

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Maina, M. B., Al-Hilaly, Y., Burra, G. B., Rickard, J., Harrington, C., Wischik, C., Serpell, L.. 2020-12-07. Oxidative stress conditions result in trapping of PHF-core tau (297-391) intermediates.. https://doi.org/10.1101/2020.12.07.414532

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