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Related Experiment Video

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Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy

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Published on: June 27, 2018

Hsp40 molecules that target to the ubiquitin-proteasome system decrease inclusion formation in models of

J L Howarth¹, S Kelly, M P Keasey

¹Henry Wellcome Laboratories for Integrated Neuroscience and Endocrinology, University of Bristol, Bristol, UK.

Molecular Therapy : the Journal of the American Society of Gene Therapy

|April 12, 2007

Summary

Heat shock protein 70 (HSP70) and DnaJ-like-1 (HSJ1) proteins reduce toxic protein inclusions in polyglutamine diseases. HSJ1 proteins enhance protein degradation via the ubiquitin-proteasome system, offering a potential therapeutic strategy.

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Last Updated: Jul 15, 2026

Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy

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Published on: June 27, 2018

Isolating Potentiated Hsp104 Variants Using Yeast Proteinopathy Models

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Purification of Hsp104, a Protein Disaggregase

Purification of Hsp104, a Protein Disaggregase

Published on: September 30, 2011

Area of Science:

Neuroscience
Molecular Biology
Genetics

Background:

Polyglutamine diseases, such as spinal and bulbar muscular atrophy (SBMA), are characterized by the formation of toxic protein inclusions.
Heat shock proteins (HSPs) are known to play roles in protein folding and degradation.

Purpose of the Study:

To investigate the efficacy of Heat Shock Protein 70 (HSP70) and DnaJ-like-1 (HSJ1) proteins in reducing polyglutamine-mediated protein inclusion formation.
To elucidate the mechanisms by which HSJ1 proteins affect protein aggregation and degradation.

Main Methods:

Expression of HSJ1 proteins, HSP70, and HSP40 in cellular and in vivo models of polyglutamine disease.
Assays to measure protein inclusion formation and protein degradation.
Analysis of ubiquitylation levels and protein complex association.

Main Results:

HSP70 and HSP40 reduced inclusion formation by promoting chaperone-mediated refolding.
HSJ1 proteins (HSJ1a and HSJ1b) significantly reduced protein inclusion formation in SBMA and neuronal models.
HSJ1 proteins increased target protein degradation via the ubiquitin-proteasome system (UPS), independent of chaperone activity.
HSJ1a expression reduced inclusions in an in vivo model of polyglutamine disease.

Conclusions:

HSJ1 proteins facilitate the degradation of misfolded proteins through the UPS.
Targeting the UPS for enhanced degradation of misfolded proteins is a promising therapeutic strategy for polyglutamine diseases.