Evidence map›Paper›PMID 38722513›Full record

ArticleMolecular neurobiology2024

C9orf72-Associated Dipeptide Repeat Expansions Perturb ER-Golgi Vesicular Trafficking, Inducing Golgi Fragmentation and ER Stress, in ALS/FTD.

Jessica Sultana, Audrey M G Ragagnin, Sonam Parakh, Sayanthooran Saravanabavan, Kai Ying Soo, Marta Vidal, Cyril Jones Jagaraj, Kunjie Ding, Sharlynn Wu, Sina Shadfar and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular neurobiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Hydrogen Sulfide Signaling in Neurodegenerative Movement Disorders.Handbook of experimental pharmacology · 2026
    Review
  4. Article
  5. Review
  6. Targeting GeneInternational journal of molecular sciences · 2025
    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

17 authors.

Jessica SultanaMotor Neuron Disease Research Centre, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
Audrey M G RagagninMotor Neuron Disease Research Centre, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
Sonam ParakhMotor Neuron Disease Research Centre, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
Sayanthooran SaravanabavanMotor Neuron Disease Research Centre, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
Kai Ying SooLa Trobe Institute for Molecular Science, La Trobe University, Bundoora, Melbourne, VIC, 3086, Australia.
Marta VidalMotor Neuron Disease Research Centre, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
Cyril Jones JagarajMotor Neuron Disease Research Centre, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
Kunjie DingMotor Neuron Disease Research Centre, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
Sharlynn WuMotor Neuron Disease Research Centre, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
Sina ShadfarMotor Neuron Disease Research Centre, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
Emily K DonMotor Neuron Disease Research Centre, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
Anand DevaDepartment of Plastic and Reconstructive Surgery, and The Integrated Specialist Healthcare Education and Research Foundation, Macquarie University, Sydney, Australia.
Garth NicholsonMotor Neuron Disease Research Centre, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
Dominic B RoweMotor Neuron Disease Research Centre, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
Ian BlairMotor Neuron Disease Research Centre, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
Shu YangMotor Neuron Disease Research Centre, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
Julie D AtkinMotor Neuron Disease Research Centre, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, 2109, Australia. julie.atkin@mq.edu.au.ORCID http://orcid.org/0000-0003-2427-499X

Funding

National Health and Medical Research Council 10305133National Health and Medical Research Council 1086887National Health and Medical Research Council 1095215National Health and Medical Research Council 1176913
6 · The paper itself

Abstract

Hexanucleotide repeat expansions (HREs) in the chromosome 9 open reading frame 72 (C9orf72) gene are the most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Both are debilitating neurodegenerative conditions affecting either motor neurons (ALS) in the brain and spinal cord or neurons in the frontal and/or temporal cortical lobes (FTD). HREs undergo repeat-associated non-ATG (RAN) translation on both sense and anti-sense strands, generating five distinct dipeptide repeat proteins (DPRs), poly-GA, -GR, -GP, -PA and -PR. Perturbed proteostasis is well-recognised in ALS pathogenesis, including processes affecting the endoplasmic reticulum (ER) and Golgi compartments. However, these mechanisms have not been well characterised for C9orf72-mediated ALS/FTD. In this study we demonstrate that C9orf72 DPRs polyGA, polyGR and polyGP (× 40 repeats) disrupt secretory protein transport from the ER to the Golgi apparatus in neuronal cells. Consistent with this finding, these DPRs also induce fragmentation of the Golgi apparatus, activate ER stress, and inhibit the formation of the omegasome, the precursor of the autophagosome that originates from ER membranes. We also demonstrate Golgi fragmentation in cells undergoing RAN translation that express polyGP. Furthermore, dysregulated ER-Golgi transport was confirmed in C9orf72 patient dermal fibroblasts. Evidence of aberrant ER-derived vesicles in spinal cord motor neurons from C9orf72 ALS patients compared to controls was also obtained. These data thus confirm that ER proteostasis and ER-Golgi transport is perturbed in C9orf72-ALS in the absence of protein over-expression. Hence this study identifies novel molecular mechanisms associated with the ER and Golgi compartments induced by the C9orf72 HRE.

Indexed as

Amyotrophic Lateral SclerosisC9orf72 ProteinDipeptidesDNA Repeat ExpansionEndoplasmic ReticulumEndoplasmic Reticulum StressFrontotemporal DementiaGolgi ApparatusHumansProtein TransportC9orf72 ProteinC9orf72 protein, humanDipeptidesALSC9orf72ER-Golgi transportER stressOmegasome

Identifiers

PMID38722513
PMCPMC11584443

What Socratic holds

Textmetadata
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 Socratic graph.