Evidence map›Paper›PMID 30344044›Full record

ArticleNeuron2018

ALS/FTD-Linked Mutation in FUS Suppresses Intra-axonal Protein Synthesis and Drives Disease Without Nuclear Loss-of-Function of FUS.

Jone López-Erauskin, Takahiro Tadokoro, Michael W Baughn, Brian Myers, Melissa McAlonis-Downes, Carlos Chillon-Marinas, Joshua N Asiaban, Jonathan Artates, Anh T Bui, Anne P Vetto and 18 more

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 143 papers.

0numbers the graph read from it
0cells of the map it votes in
143citing papers in PubMed
23.8field-weighted citation impact, top 1% of its field
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

143 citing papers in PubMed, 241 citations in OpenAlex.

  1. Article
  2. Autoimmune processes and production of catalytically active antibodies-abzymes in prone to amyotrophic lateral sclerosis FUS(1-359) mice.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Article
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  13. The Neuromuscular Junction: A Shared Vulnerability in Aging and Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Review
  14. Article
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83 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors at 6 institutions in 4 countries.

Jone López-ErauskinLudwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA.
Takahiro TadokoroDepartment of Anesthesiology, University of California at San Diego, La Jolla, CA 92093, USA.
Michael W BaughnLudwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA.
Brian MyersLudwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA.
Melissa McAlonis-DownesLudwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA.
Carlos Chillon-MarinasLudwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA.
Joshua N AsiabanLudwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA.
Jonathan ArtatesLudwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA.
Anh T BuiLudwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA.
Anne P VettoLudwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA.
Sandra K LeeLudwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA.
Ai Vy LeLudwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA.
Ying SunLudwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA.
Mélanie JambeauLudwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA.
Jihane BoubakerLudwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA.
Deborah SwingMouse Cancer Genetics Program, National Cancer Institute, Frederick, MD, 21702, USA.
Jinsong QiuDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Geoffrey G HicksRegenerative Medicine Program and Department of Biochemistry & Medical Genetics, University of Manitoba, Winnipeg, R3T 2N2, Canada.
Zhengyu OuyangDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Xiang-Dong FuDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Lino TessarolloMouse Cancer Genetics Program, National Cancer Institute, Frederick, MD, 21702, USA.
Shuo-Chien LingLudwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA.
Philippe A ParoneLudwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA.
Christopher E ShawUnited Kingdom Dementia Research Institute Centre, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, SE5 9NU London, U.K; Centre for Brain Research, University of Auckland, Auckland, New Zealand.
Martin MarsalaDepartment of Anesthesiology, University of California at San Diego, La Jolla, CA 92093, USA.
Clotilde Lagier-TourenneLudwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA; Department of Neurosciences, University of California at San Diego, La Jolla, CA 92093, USA.
Don W ClevelandLudwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA; Department of Neurosciences, University of California at San Diego, La Jolla, CA 92093, USA. Electronic address: dcleveland@ucsd.edu.
Sandrine Da CruzLudwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA. Electronic address: sdacruz@ucsd.edu.
Ludwig Cancer Research · USUniversity of California, San Diego · USCancer Genetics (United States) · USNational Cancer Institute · USUniversity of Auckland · NZUniversity of Manitoba · CA

Funding

Role of Neurotrophins in the Development of the Mammalian Nervous SystemZIABC010390 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI TESSAROLLO, LINO · 2009 to 2025
$14.2M
NEURONAL FILAMENT SYNTHESIS, ASSEMBLY, AND FUNCTIONR01NS027036 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Bogdan Bintu, Don W Cleveland · 1989 to 2026
$11.8M
U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
Training Program in Basic Clinical GeneticsT32GM008666 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAMILTON, BRUCE A · 1998 to 2021
$8.6M
Medical Research Council G0500289Medical Research Council MC_G1000733NIGMS NIH HHS T32 GM008666NINDS NIH HHS P30 NS047101NINDS NIH HHS R01 NS027036Wellcome Trust
6 · The paper itself

Abstract

Through the generation of humanized FUS mice expressing full-length human FUS, we identify that when expressed at near endogenous murine FUS levels, both wild-type and ALS-causing and frontotemporal dementia (FTD)-causing mutations complement the essential function(s) of murine FUS. Replacement of murine FUS with mutant, but not wild-type, human FUS causes stress-mediated induction of chaperones, decreased expression of ion channels and transporters essential for synaptic function, and reduced synaptic activity without loss of nuclear FUS or its cytoplasmic aggregation. Most strikingly, accumulation of mutant human FUS is shown to activate an integrated stress response and to inhibit local, intra-axonal protein synthesis in hippocampal neurons and sciatic nerves. Collectively, our evidence demonstrates that human ALS/FTD-linked mutations in FUS induce a gain of toxicity that includes stress-mediated suppression in intra-axonal translation, synaptic dysfunction, and progressive age-dependent motor and cognitive disease without cytoplasmic aggregation, altered nuclear localization, or aberrant splicing of FUS-bound pre-mRNAs. VIDEO ABSTRACT.

Indexed as

Amyotrophic Lateral SclerosisAnimalsAxonsCells, CulturedFemaleFrontotemporal DementiaHippocampusHumansLoss of Function MutationMaleMiceMice, Inbred C57BLMice, TransgenicPregnancyProtein BiosynthesisRNA-Binding Protein FUSFUS protein, mouseRNA-Binding Protein FUSALSAmyotrophic Lateral Sclerosisaxonal translationFrontotemporal dementiaFTDFUSneurodegenerative diseaseprotein synthesisRNA-binding proteinsTLS

Identifiers

PMID30344044
PMCPMC6277851
OpenAlexW2895793011

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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.