Evidence map›Paper›PMID 41318543›Full record

ArticleNature communications2025

Microgliopathy as a primary mediator of neuronal death in models of Friedreich's Ataxia.

Carla Pernaci, Avalon Johnson, Sydney Gillette, Anna S Warden, Chad McCormick, Sammy Weiser-Novak, Gabriela Ramirez, Emily H Broersma, Priyanka Mishra, Anusha Sivakumar and 2 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 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
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  5. 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

12 authors.

Carla PernaciDepartment of Pediatrics, University of California San Diego, La jolla, CA, USA.
Avalon JohnsonDepartment of Pediatrics, University of California San Diego, La jolla, CA, USA.
Sydney GilletteDepartment of Pediatrics, University of California San Diego, La jolla, CA, USA.
Anna S WardenDepartment of Pediatrics, University of California San Diego, La jolla, CA, USA.
Chad McCormickDepartment of Pediatrics, University of California San Diego, La jolla, CA, USA.
Sammy Weiser-NovakSalk Institute for Biological Studies, La Jolla, CA, USA.
Gabriela RamirezDepartment of Pediatrics, University of California San Diego, La jolla, CA, USA.
Emily H BroersmaDepartment of Pediatrics, University of California San Diego, La jolla, CA, USA.ORCID http://orcid.org/0000-0001-8540-2807
Priyanka MishraDepartment of Pediatrics, Division of Genetics, University of California San Diego, San Diego, CA, USA.
Anusha SivakumarDepartment of Pediatrics, Division of Genetics, University of California San Diego, San Diego, CA, USA.ORCID http://orcid.org/0000-0002-1366-9681
Stephanie Cherqui *Department of Pediatrics, Division of Genetics, University of California San Diego, San Diego, CA, USA.
Nicole G Coufal *Department of Pediatrics, University of California San Diego, La jolla, CA, USA. ncoufal@health.ucsd.edu.ORCID http://orcid.org/0000-0001-6547-1733

Funding

Microgial contribution and therapeutic potential in Friedreich's ataxiaR01NS135162 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Stephanie Cherqui, Nicole Gabriele Coufal · 2024 to 2026
$1.8M
Understanding the mechanism of rescue of Alzheimers disease by hematopoietic stem cell transplantationR01AG086443 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Stephanie Cherqui · 2024 to 2026
$1.2M
Incucyte Zoom Live Cell Analysis SystemS10OD025060 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WILLERT, KARL H · 2018 to 2018
$173k
California Institute for Regenerative Medicine (CIRM) EDUC2-08388California Institute for Regenerative Medicine (CIRM) TRAN1-13983Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01NS135162NIA NIH HHS R01 AG086443NIH HHS S10 OD025060NINDS NIH HHS R01 NS135162
6 · The paper itself

Abstract

Friedreich's ataxia (FRDA) is an incurable neurodegenerative disorder caused by a GAA repeat expansion in the frataxin (FXN) gene, leading to a severe reduction of the mitochondrial FXN protein, crucial for iron metabolism. While microglial inflammation is observed in FRDA, it remains unclear whether immune dysfunction is a primary disease mediator or a secondary reactionary phenotype. Utilizing patient-derived induced pluripotent stem cells (iPSCs), we report an intrinsic microglial phenotype of stark mitochondrial defects, iron overload, lipid peroxidation, and lysosomal abnormalities. These factors drive a pro-inflammatory state that contributes to neuronal death in co-culture systems. In a murine xenograft model, transplanted human FRDA microglia accumulate in white matter and the Purkinje cell layer, resulting in Purkinje neuron loss in otherwise healthy brains. Notably, CRISPR/Cas9-mediated correction of the GAA repeat reverses microglial defects and mitigates neurodegeneration. Here, we suggest that microglial dysfunction serve as a disease driver and a promising therapeutic target in FRDA.

Indexed as

Friedreich AtaxiaMicrogliaNeuronsAnimalsCell DeathCRISPR-Cas SystemsDisease Models, AnimalFemaleFrataxinHumansInduced Pluripotent Stem CellsIronIron-Binding ProteinsMaleMiceMitochondriaFrataxinIronIron-Binding Proteins

Identifiers

PMID41318543
PMCPMC12770375

What OpenQuestion holds

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LicenceCC BY
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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.