Evidence map›Paper›PMID 41213972›Full record

ArticleNature communications2025

Development of a targeted BioPROTAC degrader selective for misfolded SOD1.

Christen G Chisholm, Rachael Bartlett, Mikayla L Brown, Emma-Jayne Proctor, Natalie E Farrawell, Jody Gorman, Fabien Delerue, Lars M Ittner, Kara L Vine-Perrow, Heath Ecroyd and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Christen G ChisholmMolecular Horizons and School of Science, University of Wollongong, Wollongong, NSW, Australia. christen@uow.edu.au.ORCID http://orcid.org/0000-0002-3057-7113
Rachael BartlettMolecular Horizons and School of Science, University of Wollongong, Wollongong, NSW, Australia.ORCID http://orcid.org/0000-0002-9199-1326
Mikayla L BrownMolecular Horizons and School of Science, University of Wollongong, Wollongong, NSW, Australia.ORCID http://orcid.org/0000-0002-3464-3480
Emma-Jayne ProctorMolecular Horizons and School of Science, University of Wollongong, Wollongong, NSW, Australia.
Natalie E FarrawellMolecular Horizons and School of Science, University of Wollongong, Wollongong, NSW, Australia.
Jody GormanMolecular Horizons and School of Science, University of Wollongong, Wollongong, NSW, Australia.
Fabien DelerueDementia Research Centre, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0001-7944-2108
Lars M IttnerDementia Research Centre, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia.
Kara L Vine-PerrowMolecular Horizons and School of Science, University of Wollongong, Wollongong, NSW, Australia.ORCID http://orcid.org/0000-0001-6871-1149
Heath EcroydMolecular Horizons and School of Science, University of Wollongong, Wollongong, NSW, Australia.ORCID http://orcid.org/0000-0001-7574-0044
Neil R CashmanDjavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada.ORCID http://orcid.org/0000-0002-0080-1006
Darren N SaundersSchool of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0003-0924-0513
Luke McAlaryMolecular Horizons and School of Science, University of Wollongong, Wollongong, NSW, Australia.
Jeremy S LumMolecular Horizons and School of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, NSW, Australia. jlum@uow.edu.au.ORCID http://orcid.org/0000-0002-2133-9308
Justin J YerburyMolecular Horizons and School of Science, University of Wollongong, Wollongong, NSW, Australia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The accumulation of misfolded proteins underlies a broad range of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Due to their dynamic nature, these misfolded proteins have proven challenging to target therapeutically. Here, we specifically target misfolded disease variants of the ALS-associated protein superoxide dismutase 1 (SOD1), using a biological proteolysis targeting chimera (BioPROTAC) composed of a SOD1-specific intrabody and an E3 ubiquitin ligase. Screening of intrabodies and E3 ligases for optimal BioPROTAC construction reveals a candidate capable of degrading multiple disease variants of SOD1, preventing their aggregation in cells. Using CRISPR/Cas9 technology to develop a BioPROTAC transgenic mouse line, we demonstrate that the presence of the BioPROTAC delays disease progression in the SOD1

Indexed as

Amyotrophic Lateral SclerosisSuperoxide Dismutase-1AnimalsCRISPR-Cas SystemsDisease Models, AnimalDisease ProgressionHEK293 CellsHumansMiceMice, TransgenicMotor NeuronsProtein FoldingProteolysisUbiquitin-Protein LigasesSOD1 protein, humanSod1 protein, mouseSuperoxide Dismutase-1Ubiquitin-Protein Ligases

Identifiers

PMID41213972
PMCPMC12603324

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.