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Updated: Jul 7, 2025
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Modulation of Tau Subcellular Localization as a Tool to Investigate the Expression of Disease-related Genes
Published on: December 20, 2019
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Tridimensional Structural Analysis of Tau Isoforms Generated by Intronic Retention
Indalo Domene-Serrano1,2, Raquel Cuadros1,2, Felix Hernandez1,2
1Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain.
Journal of Alzheimer'S Disease Reports
|December 25, 2023
Summary
A newly discovered W-tau isoform may protect against neurodegenerative diseases by preventing tau aggregation. This W-tau is downregulated in conditions like Alzheimer's disease, highlighting its potential therapeutic role.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Tauopathies are neurodegenerative diseases marked by abnormal tau protein aggregates.
- A novel human-specific tau isoform, W-tau, arises from intron 12 retention.
- W-tau may possess neuroprotective qualities by inhibiting tau aggregation, but is downregulated in tauopathies.
Purpose of the Study:
- To elucidate the three-dimensional structure of W-tau.
- To investigate the conformational basis for W-tau's neuroprotective function.
- To understand W-tau's role in inhibiting tau aggregation.
Main Methods:
- Utilized a deep learning approach for predicting tau protein structures.
- Employed in vitro polymerization assays to study tau aggregation.
- Analyzed W-tau peptide interactions and effects on other tau isoforms.
Main Results:
- Predicted and compared the 3D structures of tau isoforms, including W-tau.
- Demonstrated W-tau peptide's interaction with other tau isoforms.
- Showed W-tau peptide inhibits the polymerization of other tau isoforms in vitro.
Conclusions:
- The study confirms the structure-function relationship of W-tau.
- W-tau exhibits neuroprotective behavior by inhibiting tau fibrillization.
- W-tau represents a potential therapeutic target for tauopathies.
