Evidence map›Paper›PMID 27679482›Full record

ArticleBrain : a journal of neurology2016

Exosome secretion is a key pathway for clearance of pathological TDP-43.

Yohei Iguchi, Lara Eid, Martin Parent, Geneviève Soucy, Christine Bareil, Yuichi Riku, Kaori Kawai, Shinnosuke Takagi, Mari Yoshida, Masahisa Katsuno and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Brain : a journal of neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 243 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
243citing papers in PubMed, 2 pooled it
15.3field-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

243 citing papers in PubMed, 2 syntheses or guidelines pooled it, 359 citations in OpenAlex.

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  19. Exosome Proteomics of SOD1Annals of clinical and translational neurology · 2026
    Article
  20. Article

183 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 4 institutions in 2 countries.

Yohei Iguchi1 Centre de recherche de l'Institut universitaire en santé mentale de Québec, Quebec City, Qc, Canada.
Lara Eid1 Centre de recherche de l'Institut universitaire en santé mentale de Québec, Quebec City, Qc, Canada.
Martin Parent1 Centre de recherche de l'Institut universitaire en santé mentale de Québec, Quebec City, Qc, Canada.
Geneviève Soucy1 Centre de recherche de l'Institut universitaire en santé mentale de Québec, Quebec City, Qc, Canada.
Christine Bareil1 Centre de recherche de l'Institut universitaire en santé mentale de Québec, Quebec City, Qc, Canada.
Yuichi Riku3 Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Kaori Kawai3 Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Shinnosuke Takagi3 Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Mari Yoshida4 Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Aichi, Japan.
Masahisa Katsuno3 Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Gen Sobue3 Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Jean-Pierre Julien1 Centre de recherche de l'Institut universitaire en santé mentale de Québec, Quebec City, Qc, Canada jean-pierre.julien@fmed.ulaval.ca.
Nagoya University · JPUniversité Laval · CAInstitut Universitaire en Santé Mentale de Québec · CAAichi Medical University · JP

Funding

CIHR
6 · The paper itself

Abstract

Cytoplasmic TDP-43 aggregation is a pathological hallmark of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Here we investigated the role of exosomes in the secretion and propagation of TDP-43 aggregates. TDP-43 was detected in secreted exosomes from Neuro2a cells and primary neurons but not from astrocytes or microglia. Evidence is presented that protein aggregation and autophagy inhibition are factors that promote exosomal secretion of TDP-43. We also report that levels of exosomal TDP-43 full length and C-terminal fragment species are upregulated in human amyotrophic lateral sclerosis brains. Exposure of Neuro2a cells to exosomes from amyotrophic lateral sclerosis brain, but not from control brain, caused cytoplasmic redistribution of TDP-43, suggesting that secreted exosomes might contribute to propagation of TDP-43 proteinopathy. Yet, inhibition of exosome secretion by inactivation of neutral sphingomyelinase 2 with GW4869 or by silencing RAB27A provoked formation of TDP-43 aggregates in Neuro2a cells. Moreover, administration of GW4869 exacerbated the disease phenotypes of transgenic mice expressing human TDP-43

Indexed as

Aniline CompoundsAnimalsBehavior, AnimalBenzylidene CompoundsCell LineDisease Models, AnimalDNA-Binding ProteinsExosomesHumansMiceMice, TransgenicSphingomyelin PhosphodiesteraseTDP-43 ProteinopathiesAniline CompoundsBenzylidene CompoundsDNA-Binding ProteinsGW 4869SMPD3 protein, humanSphingomyelin PhosphodiesteraseTARDBP protein, humanamyotrophic lateral sclerosisexosomeneutral sphingomyelinase 2 inhibitionTDP-43

Identifiers

PMID27679482
PMCPMC5840881
OpenAlexW2524787240

What OpenQuestion holds

Textmetadata
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.