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Related Experiment Video

Updated: Jul 13, 2025

Modulation of Tau Subcellular Localization as a Tool to Investigate the Expression of Disease-related Genes

Modulation of Tau Subcellular Localization as a Tool to Investigate the Expression of Disease-related Genes

Published on: December 20, 2019

DnaJs are enriched in tau regulators.

Abigail R Esquivel¹, Shannon E Hill¹, Laura J Blair²

¹Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA; USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL 33613, USA.

International Journal of Biological Macromolecules

|October 18, 2023

Summary

This summary is machine-generated.

Molecular chaperones, particularly from the DnaJ family like DnaJB6b, can significantly reduce toxic tau protein accumulation and seeding, offering potential therapeutic targets for neurodegenerative diseases.

Keywords:

DnaJ Molecular chaperone Tau

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Area of Science:

Neurobiology
Molecular Biology
Biochemistry

Background:

Aberrant tau protein accumulation and seeding are key pathological features in neurodegenerative diseases.
Molecular chaperones can influence tau pathology, but their roles are often studied individually.

Purpose of the Study:

To identify molecular chaperones that modulate tau seeding using a high-throughput assay.
To investigate the specific effects of identified chaperones on tau pathology.

Main Methods:

A semi-high throughput FRET biosensor assay using Tau RD P301S cells was employed.
Approximately fifty chaperones were screened for their effects on tau seeding via live cell imaging.
Overexpression and knockdown (shRNA) studies were conducted for key chaperones.

Main Results:

Five chaperones significantly affected tau seeding, with three from the DnaJ family showing notable impact.
Overexpression of DnaJA2, DnaJB1, and DnaJB6b reduced tau levels; knockdown of DnaJB1 and DnaJB6b showed an inverse correlation with tau levels.
DnaJB6b specifically reduced total tau levels, partly via enhanced proteasomal degradation, and interacted with tau complexes.

Conclusions:

The DnaJ family of molecular chaperones, especially DnaJB6b, exhibits potent activity in modulating tau pathology.
DnaJB6b's ability to reduce tau levels and interact with tau complexes suggests its therapeutic potential in tauopathies.