Shapeshifter W-Tau Peptide Inhibits Tau Aggregation and Disintegrates Paired Helical Filaments.

ABSTRACT: Tauopathies comprise a range of neurodegenerative conditions characterized by the aberrant accumulation of tau protein clumps in the brain. These aggregates are formed by different tau splicing isoforms. Here, we analyzed the role of a specific intron-derived peptide called the W-Tau peptide on the polymerization-depolymerization of tau filaments. This peptide originates from a new isoform of the tau protein, named W-Tau, which is formed due to the retention of intron 12. AlphaFold3 (AF3)-based in silico investigations suggested that the W-Tau peptide interacts with tau monomers. Our in vitro experiments confirmed these predictions and showed that the W-Tau peptide inhibited tau aggregation. In addition, the W-Tau peptide disrupted preexisting paired helical filaments (PHFs)

SUBMITTER: Domene-Serrano I 

PROVIDER: S-EPMC12004447 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature