Evidence map›Paper›PMID 30711519›Full record

ArticleEBioMedicine2019

Micro-RNAs secreted through astrocyte-derived extracellular vesicles cause neuronal network degeneration in C9orf72 ALS.

André Varcianna, Monika A Myszczynska, Lydia M Castelli, Brendan O'Neill, Yeseul Kim, Jordan Talbot, Sophie Nyberg, Immanuelle Nyamali, Paul R Heath, Matthew J Stopford and 2 more

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers.

0numbers the graph read from it
0cells of the map it votes in
139citing papers in PubMed
16.4field-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

139 citing papers in PubMed, 188 citations in OpenAlex.

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  16. Antisense oligonucleotide depletion ofmedRxiv : the preprint server for health sciences · 2025
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79 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

12 authors at 1 institution in 1 country.

André VarciannaSheffield Institute of Translational Neuroscience (SITraN), University of Sheffield, 385A Glossop Road, Sheffield S10 2HQ, UK.
Monika A MyszczynskaSheffield Institute of Translational Neuroscience (SITraN), University of Sheffield, 385A Glossop Road, Sheffield S10 2HQ, UK.
Lydia M CastelliSheffield Institute of Translational Neuroscience (SITraN), University of Sheffield, 385A Glossop Road, Sheffield S10 2HQ, UK.
Brendan O'NeillSheffield Institute of Translational Neuroscience (SITraN), University of Sheffield, 385A Glossop Road, Sheffield S10 2HQ, UK.
Yeseul KimSheffield Institute of Translational Neuroscience (SITraN), University of Sheffield, 385A Glossop Road, Sheffield S10 2HQ, UK.
Jordan TalbotSheffield Institute of Translational Neuroscience (SITraN), University of Sheffield, 385A Glossop Road, Sheffield S10 2HQ, UK.
Sophie NybergSheffield Institute of Translational Neuroscience (SITraN), University of Sheffield, 385A Glossop Road, Sheffield S10 2HQ, UK.
Immanuelle NyamaliSheffield Institute of Translational Neuroscience (SITraN), University of Sheffield, 385A Glossop Road, Sheffield S10 2HQ, UK.
Paul R HeathSheffield Institute of Translational Neuroscience (SITraN), University of Sheffield, 385A Glossop Road, Sheffield S10 2HQ, UK.
Matthew J StopfordSheffield Institute of Translational Neuroscience (SITraN), University of Sheffield, 385A Glossop Road, Sheffield S10 2HQ, UK.
Guillaume M HautbergueSheffield Institute of Translational Neuroscience (SITraN), University of Sheffield, 385A Glossop Road, Sheffield S10 2HQ, UK.
Laura FerraiuoloSheffield Institute of Translational Neuroscience (SITraN), University of Sheffield, 385A Glossop Road, Sheffield S10 2HQ, UK. Electronic address: l.ferraiuolo@sheffield.ac.uk.
University of Sheffield · GB

Funding

Medical Research Council MR/R024162/1Motor Neurone Disease Association HAUTBERGUE/APR16/846-791
6 · The paper itself

Abstract

backgroundAstrocytes regulate neuronal function, synaptic formation and maintenance partly through secreted extracellular vesicles (EVs). In amyotrophic lateral sclerosis (ALS) astrocytes display a toxic phenotype that contributes to motor neuron (MN) degeneration.

methodsWe used human induced astrocytes (iAstrocytes) from 3 ALS patients carrying C9orf72 mutations and 3 non-affected donors to investigate the role of astrocyte-derived EVs (ADEVs) in ALS astrocyte toxicity. ADEVs were isolated from iAstrocyte conditioned medium via ultracentrifugation and resuspended in fresh astrocyte medium before testing ADEV impact on HB9-GFP

findingsWe report that EV formation and miRNA cargo are dysregulated in C9ORF72-ALS iAstrocytes and this affects neurite network maintenance and MN survival in vitro. In particular, we have identified downregulation of miR-494-3p, a negative regulator of semaphorin 3A (SEMA3A) and other targets involved in axonal maintenance. We show here that by restoring miR-494-3p levels through expression of an engineered miRNA mimic we can downregulate Sema3A levels in MNs and increases MN survival in vitro. Consistently, we also report lower levels of mir-494-3p in cortico-spinal tract tissue isolated from sporadic ALS donors, thus supporting the pathological importance of this pathway in MNs and its therapeutic potential.

interpretationALS ADEVs and their miRNA cargo are involved in MN death in ALS and we have identified miR-494-3p as a potential therapeutic target.

fundingThierry Latran Fondation and Academy of Medical Sciences.

Indexed as

AdultAgedAmyotrophic Lateral SclerosisAnimalsAstrocytesAutopsyBiopsyC9orf72 ProteinCell SurvivalCulture Media, ConditionedDisease Models, AnimalDisease SusceptibilityExtracellular VesiclesFemaleGene Expression ProfilingGene Expression RegulationC9orf72 ProteinCulture Media, ConditionedMicroRNAsSEMA3A protein, humanSemaphorin-3AAmyotrophic lateral sclerosisAstrocytesAxonal growthExtracelular vesiclesGene therapymiRNANeurodegeneration

Identifiers

PMID30711519
PMCPMC6413467
OpenAlexW2911503339

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.