A proteomic analysis of the PHF-forming tau fragment (tau297-391) following uptake into differentiated human neuronal SHSY5Y cells.

Alice Copsey; Sebastian S Oakley; Mahmoud B Maina; Robert Parker; Karen E Marshall; Charles R Harrington; John M D Storey; Claude M Wischik; Louise C Serpell

doi:10.1042/bsr20260349

PubMed · 42627127

A proteomic analysis of the PHF-forming tau fragment (tau297-391) following uptake into differentiated human neuronal SHSY5Y cells.

Alice Copsey·Sebastian S Oakley·Mahmoud B Maina·Robert Parker·Karen E Marshall·Charles R Harrington·John M D Storey·Claude M Wischik·Louise C Serpell

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Abstract

Tau self-assembly and intracellular deposition are associated with a group of neurodegenerative diseases called tauopathies, which include Alzheimer's disease (AD) and Pick's disease. Here, we measured the proteome response in human neuronal cells (differentiated SH-SY5Y) following the addition of a spontaneously amyloidogenic region of tau known as dGAE (tau297-391), which forms AD-like paired helical filaments in vitro, and proteomic analysis showed increased endogenous tau expression. Further interactome analysis uncovered increased association between tau and proteins associated with nuclear chromatin, the nucleolus, and the spliceosome, as well as the thiol-peroxidase, PRDX6, alongside an increase in reactive oxygen species. The present work highlights a method to identify proteome pathways that may play an important role in the development of tau pathology and reveals an oxidative stress response to dGAE.

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Humans tau Proteins Proteomics Neurons Cell Line, Tumor Cell Differentiation Oxidative Stress Reactive Oxygen Species Tauopathies Proteome Peptide Fragments Alzheimer's Disease PDRX6 proteome tau proteins tauopathies Journal Article

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Alice Copsey, Sebastian S Oakley, Mahmoud B Maina, Robert Parker, Karen E Marshall, Charles R Harrington, John M D Storey, Claude M Wischik, Louise C Serpell. 2026-09-16. A proteomic analysis of the PHF-forming tau fragment (tau297-391) following uptake into differentiated human neuronal SHSY5Y cells.. https://doi.org/10.1042/bsr20260349

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