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Exosome secretion is a key pathway for clearance of pathological TDP-43
Iguchi Y, Eid L, Parent M, Soucy G, Bareil C, Riku Y, Kawai K, Takagi S et al.. Brain : a journal of neurology, 2016-09-27
Topic: Brain proteins, microglia and lab models
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 A315T mutant. Thus, even though results suggest that exosomes containing pathological TDP-43 may play a key role in the propagation of TDP-43 proteinopathy, a therapeutic strategy for amyotrophic lateral sclerosis based on inhibition of exosome production would seem inappropriate, as in vivo data suggest that exosome secretion plays an overall beneficial role in neuronal clearance of pathological TDP-43.
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APA 7th
Iguchi, Y., Eid, L., Parent, M., Soucy, G., Bareil, C., Riku, Y., et al. (2016). Exosome secretion is a key pathway for clearance of pathological TDP-43. Brain : a journal of neurology. https://doi.org/10.1093/brain/aww237
Vancouver
Iguchi Y, Eid L, Parent M, Soucy G, Bareil C, Riku Y, et al. Exosome secretion is a key pathway for clearance of pathological TDP-43. Brain : a journal of neurology. 2016. doi:10.1093/brain/aww237. PMID: 27679482.
BibTeX
@article{iguchi2016-27679482,
author = {Iguchi, Y. and Eid, L. and Parent, M. and Soucy, G. and Bareil, C. and Riku, Y. and Kawai, K. and Takagi, S. and others},
title = {{Exosome secretion is a key pathway for clearance of pathological TDP-43}},
journal = {Brain : a journal of neurology},
year = {2016},
doi = {10.1093/brain/aww237},
pmid = {27679482},
url = {https://doi.org/10.1093/brain/aww237}
}
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Key findings
- 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.
- Thus, even though results suggest that exosomes containing pathological TDP-43 may play a key role in the propagation of TDP-43 proteinopathy, a therapeutic strategy for amyotrophic lateral sclerosis based on inhibition of exosome production would seem inappropriate, as in vivo data suggest that exosome secretion plays an overall beneficial role in neuronal clearance of pathological TDP-43.
Why it matters
This study found that exosomes may help spread pathological TDP-43, but that blocking exosome production worsened disease in mice, suggesting that inhibiting exosomes would not be a good therapeutic strategy. It is an animal and cell study and does not test any treatment or prevention for Alzheimer's disease, so it has no direct implications for treating, curing, or preventing the disease.
Study details
- Evidence strengthLow
How this study scored 50/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 360 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 30.0 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 4 / 6 | Cited 14.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 9 other studies in this library |
| Still being cited | 3 / 4 | Cited 112 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Jean-Pierre Julien: h-index 15 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Université Laval: institution h-index 823 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27679482) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 50 / 100 | — |
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