Evidence map›Paper›PMID 41691309›Full record

ArticleMolecular neurodegeneration2026

Impaired nucleocytoplasmic transport in SOD1-mediated ALS.

Shirel Argueti-Ostrovsky, Su Min Lim, Olubankole A Arogundade, Sandra Diaz-Garcia, Gulshan Yunisova, Alex Meng, Anita Hermann, Kailee Ong, Ekaterina Eremenko, Mariana Bravo-Hernandez and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular neurodegeneration, 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

23 authors.

Shirel Argueti-Ostrovsky *Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O.B. 653 84105, Beer Sheva, Israel.
Su Min Lim *Department of Neurology, the Sean M. Healey and AMG Center for ALS at Mass General, Massachusetts General Brigham, Harvard Medical School, Boston, MA, 02114, USA.
Olubankole A ArogundadeDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, 92093, USA.
Sandra Diaz-GarciaDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, 92093, USA.
Gulshan YunisovaDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, 92093, USA.
Alex MengDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, 92093, USA.
Anita HermannDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, 92093, USA.
Kailee OngDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, 92093, USA.
Ekaterina EremenkoThe Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Mariana Bravo-HernandezDepartment of Anesthesiology, School of Medicine, University of California San Diego, San Diego, CA, USA.
Shawn P DriscollGene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA, USA.
Chao-Zong LeeDepartment of Neurology, the Sean M. Healey and AMG Center for ALS at Mass General, Massachusetts General Brigham, Harvard Medical School, Boston, MA, 02114, USA.
Xin JiangDepartment of Neurology, the Sean M. Healey and AMG Center for ALS at Mass General, Massachusetts General Brigham, Harvard Medical School, Boston, MA, 02114, USA.
Alexandra StavskyDepartment of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O.B. 653 84105, Beer Sheva, Israel.
Shir BarelDepartment of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O.B. 653 84105, Beer Sheva, Israel.
Tom ShaniDepartment of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O.B. 653 84105, Beer Sheva, Israel.
Joy KahnDepartment of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O.B. 653 84105, Beer Sheva, Israel.
Samuel L PfaffGene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA, USA.
Alon MonsonegoThe Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Martin MarsalaDepartment of Anesthesiology, School of Medicine, University of California San Diego, San Diego, CA, USA.
John RavitsDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, 92093, USA.
Clotilde Lagier-TourenneDepartment of Neurology, the Sean M. Healey and AMG Center for ALS at Mass General, Massachusetts General Brigham, Harvard Medical School, Boston, MA, 02114, USA. clagier-tourenne@mgh.harvard.edu.
Adrian IsraelsonDepartment of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O.B. 653 84105, Beer Sheva, Israel. adriani@bgu.ac.il.

Funding

Multimodal analysis and therapeutic targeting of aberrant nucleocytoplasmic compartmentalization in FUS-related neurodegenerative diseaseR01NS108769 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Daryl Angela Bosco, Ankur Jain · 2019 to 2026
$5.2M
Binational Science Foundation 217118NINDS NIH HHS R01 NS108769
6 · The paper itself

Abstract

backgroundImpaired nucleocytoplasmic transport (NCT) has emerged as a shared pathogenic mechanism in various neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). Although mutations in the gene encoding superoxide dismutase 1 (SOD1) account for approximately 20% of familial ALS cases, the impact of mutant SOD1 accumulation on the NCT remains unclear.

methodsUtilizing in vitro and in vivo models, patient-derived fibroblasts, and postmortem spinal cord tissues from ALS patients with SOD1 mutations, we determined the effects of mutant SOD1 on NCT dynamics, nuclear morphology and cellular localization of transport receptors and nuclear pore components.

resultsMutant SOD1 disrupts nuclear import and export trafficking, causing cytosolic accumulation of key transport regulators such as RanGAP1 and exportin 1 (XPO1). Mutant SOD1 also lowers the abundance of FG-Nups at the nuclear pore without altering nuclear circularity. Abnormal accumulation of NCT components was identified in Iba1-positive microglia, indicating a previously overlooked, non-cell-autonomous contribution to disease pathogenesis. Importantly, AAV-mediated reduction of mutant SOD1 in transgenic mice restored nuclear XPO1 localization, underscoring the causal role of mutant SOD1 in NCT abnormalities. Finally, comparable NCT perturbations were observed in patient-derived fibroblasts and in post-mortem spinal cord tissues from individuals with SOD1-ALS.

conclusionsOur results implicate NCT disruption as a shared disease mechanism between SOD1-mediated ALS and other familial and sporadic forms of ALS, adding support for targeting this pathway as an attractive therapeutic strategy in this fatal disease.

Indexed as

Active Transport, Cell NucleusAmyotrophic Lateral SclerosisSuperoxide Dismutase-1AnimalsExportin 1 ProteinFibroblastsHumansMiceMice, TransgenicMutationSpinal CordExportin 1 ProteinSOD1 protein, humanSuperoxide Dismutase-1ALSMisfolded SOD1NeurodegenerationNuclear pore complexNucleocytoplasmic transportNucleoporinsRanGAP1XPO1

Identifiers

PMID41691309
PMCPMC12922372

What Socratic holds

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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 Socratic graph.