Evidence map›Paper›PMID 27551461›Full record

ArticleCell death discovery2015

ALS-associated mutant FUS inhibits macroautophagy which is restored by overexpression of Rab1.

K Y Soo, J Sultana, A E King, Rak Atkinson, S T Warraich, V Sundaramoorthy, I Blair, M A Farg, J D Atkin

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death discovery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

34 citing papers in PubMed, 64 citations in OpenAlex.

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  12. Molecular therapy. Nucleic acids · 2021
    Article
  13. Review
  14. Article
  15. Molecular and Cellular Mechanisms Affected in ALS.Journal of personalized medicine · 2020
    Review
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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

9 authors at 3 institutions in 1 country.

K Y SooDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University , Bundoora, Victoria, Australia.
J SultanaDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University , North Ryde, New South Wales, Australia.
A E KingWicking Dementia Research and Education Centre, University of Tasmania , Hobart, Tasmania, Australia.
Rak AtkinsonWicking Dementia Research and Education Centre, University of Tasmania , Hobart, Tasmania, Australia.
S T WarraichDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University , North Ryde, New South Wales, Australia.
V SundaramoorthyDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University , North Ryde, New South Wales, Australia.
I BlairDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University , North Ryde, New South Wales, Australia.
M A FargDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University , Bundoora, Victoria, Australia.
J D AtkinDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University , North Ryde, New South Wales, Australia.
Macquarie University · AULa Trobe University · AUUniversity of Tasmania · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Amyotrophic lateral sclerosis (ALS) is characterised by the formation of intracellular misfolded protein inclusions that form in motor neurons. Autophagy is the major degradation pathway for aggregate-prone proteins within lysosomes. Autophagy begins by the production of the omegasome, forming the autophagosome membrane, which then fuses with the lysosome. Mutations in fused in sarcoma (FUS) cause 5% of familial ALS cases and FUS-positive inclusions are also formed in sporadic ALS tissues. In this study, we demonstrate that the expression of ALS-associated mutant FUS impairs autophagy in neuronal cells. In mutant FUS-expressing neuronal cells, accumulation of ubiquitinated proteins and autophagy substrates p62 and NBR1 was detected, and formation of both the omegasome and autophagosome was inhibited in these cells. However, overexpression of Rab1 rescued these defects, suggesting that Rab1 is protective in ALS. The number of LC3-positive vesicles was also increased in motor neurons from the spinal cord of an ALS patient carrying a FUS (R521C) mutation compared with a control patient, providing additional evidence that autophagy is dysregulated in mutant FUS-associated ALS. This study provides further understanding of the intricate autophagy system and neurodegeneration in ALS.

Identifiers

PMID27551461
PMCPMC4979432
OpenAlexW2245720596

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.