Evidence map›Paper›PMID 41746753›Full record

ArticleThe Journal of clinical investigation2026

Disruption of CSF-1 receptor-mediated metal ion homeostasis in the murine brain promotes neurodegenerative disease.

Violeta Chițu, Julia Alvarenga, Wenna Chen, David Reynolds, Yang Liu, Daqian Sun, Anders Sandell, Virginjia Danylaité-Karrenbauer, Per Uvdal, Iran An da Silva and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

20 authors.

Violeta ChițuDepartment of Developmental and Molecular Biology.
Julia AlvarengaDepartment of Developmental and Molecular Biology.
Wenna ChenDepartment of Genetics, and.
David ReynoldsDepartment of Genetics, and.
Yang LiuDepartment of Genetics, and.
Daqian SunDepartment of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, USA.
Anders SandellDivision of X-ray Photon Science, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden.
Virginjia Danylaité-KarrenbauerDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Per UvdalChemical Physics, Department of Chemistry.
Iran An da SilvaNanoLund.
Christophe SandtSynchrotron SOLEIL, Saint-Aubin, France.
Oxana KlementievaNanoLund.
Ulf JohanssonMAX IV Laboratory, Lund University, Lund, Sweden.
Kavitha Subramanian VigneshDivision of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
Zbigniew K WszolekDepartment of Neurology and.
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Jennifer T AguilianDepartment of Pathology.
Simone SidoliDepartment of Biochemistry, and.
Deyou ZhengDepartment of Genetics, and.
E Richard StanleyDepartment of Developmental and Molecular Biology.

Funding

SUPPORT FOR THE ROSE F KENNEDY IDDRC P50P50HD105352 · NICHD · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI SOPHIE MOLHOLM, Steven Upshaw Walkley · 2021 to 2026
$7.0M
Orbitrap Exploris 480 Basic SystemS10OD030286 · OD · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI SIDOLI, SIMONE · 2021 to 2021
$600k
NICHD NIH HHS P50 HD105352NIH HHS S10 OD030286
6 · The paper itself

Abstract

Dominant-inactivating mutations in the colony stimulating factor-1 receptor (CSF1R) cause CSF-1R-related leukoencephalopathy (CRL), an adult-onset neurodegenerative disease that is modeled in the Csf1r+/- mouse. CRL is caused by microglial dysfunction. However, the primary microglial deficit is unknown. To address this question, we employed single-nucleus RNA sequencing of brains from young Csf1r+/- mice without pathological or behavioral alterations. Reduction of CSF-1R signaling caused metal ion accumulation in brain macrophages, with concomitant activation of cell death and stress response pathways in oligodendrocytes and neuronal subpopulations. Reduction of metallothionein 1 (Mt1) and 3 (Mt3) gene expression was a common feature in glial and neuronal cells of Csf1r+/- mice. Overexpression of Mt1 restored metal ion homeostasis, normalized ROS production in microglia, and prevented the development of behavioral deficits, while Mt3 deletion had disease-enhancing effects. These findings demonstrate CSF-1R regulation of metal ion homeostasis via metallothioneins in the brain.

Indexed as

BrainHomeostasisMetalsNeurodegenerative DiseasesReceptors, Granulocyte-Macrophage Colony-Stimulating FactorAnimalsMetallothioneinMetallothionein 3MiceMice, KnockoutMicrogliaNeuronsOligodendrogliaSignal TransductionCsf1r protein, mouseMetallothioneinmetallothionein-1, mouseMetallothionein 3MetalsMt3 protein, mouseReceptors, Granulocyte-Macrophage Colony-Stimulating FactorCell biologyDemyelinating disordersNeuroscience

Identifiers

PMID41746753
PMCPMC13132378

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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.