Tridimensional Structural Analysis of Tau Isoforms Generated by Intronic Retention.
Resumen: Background: Tauopathies are a subset of neurodegenerative diseases characterized by abnormal tau inclusions. Recently, we
have discovered a new, human specific, tau isoform termedW-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 in vitro polymerization assay was included to accurately
predict, analyze, and understand tau protein structure and the conformational basis for the neuroprotective role of W-tau.
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 in vitro.
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