Tridimensional Structural Analysis of Tau Isoforms Generated by Intronic Retention.

Background

Tauopathies are a subset of neurodegenerative diseases characterized by abnormal tau inclusions. Recently, we have discovered a new, human specific, tau isoform termed W-tau that originates by intron 12 retention. Our preliminary data suggests this newly discovered W-tau isoform might prevent aberrant aggregation of other tau isoforms but is significantly downregulated in tauopathies such as Alzheimer's disease.

Objective

To accurately predict, examine, and understand tau protein structure and the conformational basis for the neuroprotective role of W-tau.

Methods

A tridimensional deep learning-based approach and

Results

Our findings demonstrate: a) the predicted protein tridimensionality structure of the tau isoforms raised by intron retention and their comparison with the other tau isoforms; b) the interaction of W-tau peptide (from W-tau isoform) with other tau isoforms; c) the effect of W-tau peptide in the polymerization of those tau isoforms.

Conclusions

This study supports the importance of the structure-function relationship on the neuroprotective behavior of W-tau inhibiting tau fibrillization

Informations de copyright

© 2023 – The authors. Published by IOS Press.

Déclaration de conflit d'intérêts

Jesus Avila is an Editorial Board Member of this journal but was not involved in the peer-review process nor had access to any information regarding its peer-review.