Evidence map›Paper›PMID 40501854›Full record

ArticlebioRxiv : the preprint server for biology2025

Double strand breaks drive toxicity in Huntington's disease mice with or without somatic expansion.

Aris A Polyzos, Ana Cheong, Jung Hyun Yoo, Lana Blagec, Zachary D Nagel, Cynthia T McMurray

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Aris A PolyzosDivision of Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA USA 94720.ORCID 0000-0002-9542-5807
Ana CheongDepartment of Environmental Health, John B Little Centre of Radiation Sciences, Harvard T.H. Chan School of Public Health, Boston, MA USA 02115.
Jung Hyun YooDivision of Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA USA 94720.
Lana BlagecDivision of Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA USA 94720.ORCID 0009-0001-4683-7821
Zachary D NagelDepartment of Environmental Health, John B Little Centre of Radiation Sciences, Harvard T.H. Chan School of Public Health, Boston, MA USA 02115.
Cynthia T McMurrayDivision of Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA USA 94720.

Funding

Chemical FingerprintingR01NS060115 · NINDS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI POLYZOS, ARIS A · 2007 to 2024
$7.7M
Multi-Pathway DNA Repair Capacity Measurements in Lung Cancer Patients and Healthy ControlsU01ES029520 · NIEHS · HARVARD SCHOOL OF PUBLIC HEALTH · PI CHRISTIANI, DAVID C, ENGELWARD, BEVIN P. · 2018 to 2022
$3.3M
Mismatch Repair and DNA expansionR01GM066359 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI MCMURRAY, CYNTHIA THERESE · 2004 to 2011
$2.9M
NIEHS NIH HHS U01 ES029520NIGMS NIH HHS R01 GM066359NINDS NIH HHS R01 NS060115
6 · The paper itself

Abstract

There has been a substantial investment in elucidating the mechanism of expansion in hopes of identifying therapeutic targets for Huntington disease (HD). Although an expanded CAG allele is the causal mutation for HD, there is evidence that somatic expansion may not be the only disease driver. We report here that double strand breaks (DSBs) drive HD toxicity by an independent mechanism from somatic expansion. The mutant HD protein inhibits non-homologous end joining (NHEJ) activity, leading to the accumulation of DSBs. DSBs promote transcriptional pathology in mice that cannot expand their CAG tracts somatically. Conversely, Inhibition of DSBs reverses neuronal toxicity in animals that undergo somatic expansion. Although they coexist in neurons, DSBs and somatic expansion are independent therapeutic targets for HD.

Identifiers

PMID40501854
PMCPMC12154654

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Registered trials

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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.