Evidence map›Paper›PMID 30120348›Full record

ReviewNature reviews. Neurology2018

C9orf72-mediated ALS and FTD: multiple pathways to disease.

Rubika Balendra, Adrian M Isaacs

Open access · greenAbstract readReview
In one paragraph

Review in Nature reviews. Neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 445 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
445citing papers in PubMed, 4 pooled it
48.4field-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

445 citing papers in PubMed, 4 syntheses or guidelines pooled it, 715 citations in OpenAlex.

  1. The prevalence of frontotemporal dementia: a systematic review and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Pooled it
  2. Pooled it
  3. Pooled it
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  5. Article
  6. Review
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  8. Wild-type C9orf72 drives proteasomal dysfunction and mutant aggregates via a Stat1-Isg15 axis in Huntington's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
  9. Article
  10. RAN Translation-Coupled Decay of theInternational journal of molecular sciences · 2026
    Article
  11. Review
  12. Article
  13. Article
  14. LINE-1 Retrotransposons and Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2026
    Review
  15. Article
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  17. Article
  18. Article
  19. Intrathecal (GActa neuropathologica communications · 2026
    Article
  20. Review

385 more citing papers are in PubMed but not listed here.

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

2 authors at 1 institution in 1 country.

Rubika BalendraDepartment of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
Adrian M IsaacsDepartment of Neurodegenerative Disease, UCL Institute of Neurology, London, UK. a.isaacs@ucl.ac.uk.
University College London · GB

Funding

European Research Council 648716Motor Neurone Disease Association ISAACS/APR15/834-791Wellcome Trust 107196
6 · The paper itself

Abstract

The discovery that repeat expansions in the C9orf72 gene are a frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) has revolutionized our understanding of these diseases. Substantial headway has been made in characterizing C9orf72-mediated disease and unravelling its underlying aetiopathogenesis. Three main disease mechanisms have been proposed: loss of function of the C9orf72 protein and toxic gain of function from C9orf72 repeat RNA or from dipeptide repeat proteins produced by repeat-associated non-ATG translation. Several downstream processes across a range of cellular functions have also been implicated. In this article, we review the pathological and mechanistic features of C9orf72-associated FTD and ALS (collectively termed C9FTD/ALS), the model systems used to study these conditions, and the probable initiators of downstream disease mechanisms. We suggest that a combination of upstream mechanisms involving both loss and gain of function and downstream cellular pathways involving both cell-autonomous and non-cell-autonomous effects contributes to disease progression.

Indexed as

Amyotrophic Lateral SclerosisC9orf72 ProteinDisease Models, AnimalFrontotemporal DementiaAnimalsHumansC9orf72 ProteinC9orf72 protein, human

Identifiers

PMID30120348
PMCPMC6417666
OpenAlexW2887838825

What OpenQuestion holds

Textmetadata
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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.