Journal article
Extracellular vesicles in TDP-43 proteinopathies: pathogenesis and biomarker potential
- Abstract:
- Extracellular vesicles (EVs) are membrane-enclosed nanoparticles released by most cell types, and from multiple sub-cellular compartments. They carry a range of cargo biomolecules, including protein and RNA that reflect the type and status of their cell of origin. EVs are associated with the 43 kDa trans-active response DNA binding protein (TDP-43), aggregates of which are a key pathological feature across the spectrum of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other TDP-43 proteinopathies. The secretion of TDP-43 via EVs may have beneficial effects through the cellular clearance of aggregated protein, or detrimental effects via the intercellular spread of templated TDP-43 aggregation. This review examines evidence for the association of TDP-43 with EVs in post mortem tissue, in vitro models and human biofluids, and discusses evidence for EV TDP-43 involvement in pathogenesis via clearance or ‘seeding’ processes. We further discuss the potential for use of EVs in biomarker development, through analysis of TDP-43 or alternative protein and RNA cargoes.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Version of record, pdf, 2.2MB, Terms of use)
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- Publisher copy:
- 10.1186/s13024-025-00859-4
Authors
+ Motor Neurone Disease Association
More from this funder
- Funder identifier:
- https://ror.org/02gq0fg61
- Funding agency for:
- Thompson, AG
- Grant:
- Thompson/Jan20/952 − 795
- Programme:
- Lady Edith Wolfson Clinician Scientist Fellowship
+ Medical Research Council
More from this funder
- Funder identifier:
- https://ror.org/03x94j517
- Funding agency for:
- Thompson, AG
- Grant:
- MR/T006927/1
- Publisher:
- BioMed Central
- Journal:
- Molecular Neurodegeneration More from this journal
- Volume:
- 20
- Issue:
- 1
- Article number:
- 68
- Publication date:
- 2025-06-10
- Acceptance date:
- 2025-06-03
- DOI:
- EISSN:
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1750-1326
- Language:
-
English
- Keywords:
- Pubs id:
-
2128162
- Local pid:
-
pubs:2128162
- Deposit date:
-
2025-06-05
- ARK identifier:
Terms of use
- Copyright holder:
- Dellar et al.
- Copyright date:
- 2025
- Rights statement:
- © The Author(s) 2025. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
- Licence:
- CC Attribution (CC BY)
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