Article

Tuning Hsp104 specificity to selectively detoxify α-synuclein

2020-04-16

Abstract excerpt

<h4>Summary</h4> Hsp104 is an AAA+ protein disaggregase that solubilizes and reactivates proteins trapped in aggregated states. We have engineered potentiated Hsp104 variants to mitigate toxic misfolding of α-synuclein, TDP-43, and FUS implicated in fatal neurodegenerative disorders. Though potent disaggregases, these enhanced Hsp104 variants lack substrate specificity, and can have unfavorable off-target effects...

Topics

Open a Topic to create a Post that cites this publication.

Identifiers and source

Literature Corpus work: 43e15521-921c-57d3-8650-90f53c8332ef
DOI: 10.1101/2020.04.15.043935

Open publication

Related research

Semantic proximity does not establish scientific evidence.

Click a neighbor to travelStep 1 · 12 closest

Tuning Hsp104 specificity to selectively detoxify α-synucleinDOI 10.1101/2020.04.15.043935Read

Therapeutic genetic variation revealed in diverse Hsp104 homologs.Semantic proximity Read

Therapeutic genetic variation revealed in diverse Hsp104 homologsSemantic proximity Read

High-throughput screening approach identifies substrate-selective Hsp104 variants that counter amyloid seeding with diminished off-target effects.Semantic proximity Read

Potentiated Hsp104 variants suppress toxicity of diverse neurodegenerative disease-linked proteins.Semantic proximity Read

HSP110 dependent HSP70 disaggregation machinery mediates prion-like propagation of amyloidogenic proteins in metazoaSemantic proximity Read

Design principles to tailor Hsp104 therapeuticsSemantic proximity Read

Hsp110 mitigates α-synuclein pathology in vivoSemantic proximity Read

Effect of endogenous Hsp104 chaperone in yeast models of sporadic and familial Parkinson's disease.Semantic proximity Read

Structural polymorphism of α-synuclein fibrils alters pathway of Hsc70 mediated disaggregationSemantic proximity Read

PRO-FitS: a novel phenotypic assay to identify enhancers of proteostasis in <i>C. elegans</i>Semantic proximity Read

A targetable N-terminal motif orchestrates α-Synuclein oligomer to fibril conversionSemantic proximity Read

The Hsp104 N-terminal domain enables disaggregase plasticity and potentiation.Semantic proximity Read