Extracellular vesicles – Their role in the packaging and spread of misfolded proteins associated with neurodegenerative diseases
Abstract
Many cell types, including neurons, are known to release small membranous vesicles known as exosomes. In addition to their protein content these vesicles have recently been shown to contain messenger RNA (mRNA) and micro RNA (miRNA) species. Roles for these vesicles include cell-cell signalling, removal of unwanted proteins, and transfer of pathogens (including prion-like misfolded proteins) between cells, such as infectious prions. Prions are the infectious particles that are responsible for transmissible neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD) of humans or bovine spongiform encephalopathy (BSE) of cattle. Exosomes are also involved in processing the amyloid precursor protein (APP), which is associated with Alzheimer's disease (AD). As exosomes can be isolated from circulating fluids such as serum, urine, and cerebrospinal fluid (CSF), they provide a potential source of biomarkers for neurological conditions. Here, we review the roles these vesicles play in neurodegenerative disease and highlight their potential in diagnosing these disorders through analysis of their RNA content.
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Recent research has highlighted the significant role of sEVs in the propagation of misfolded proteins in neurodegenerative diseases, suggesting they may facilitate intercellular transfer and contribute to the progression and severity of these conditions.
“Recent research has highlighted the significant role of sEVs in the propagation of these misfolded proteins, suggesting they may facilitate intercellular transfer and contribute to the progression and severity of these conditions [130–132].”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [130]
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BackgroundZhou, J., Benito‐Martín, A., Mighty, J., Chang, L., Ghoroghi, S., Wu, H., Wong, M., Guariglia, S. R., Baranov, P. Y., Young, M. J., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-20421-1 · Cited by 59 · see citing works
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“The latter two can be shed directly from the plasma membrane; however, exosomes need to be released upon fusion of MVBs with the plasma membrane (Coleman and Hill, 2015).”
BackgroundHu, G., Yang, L., Cai, Y. C., Niu, F., Mezzacappa, F., Callen, S. E., Fox, H. S., & Buch, S. J. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.336 · Cited by 59 · see citing works
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“EVs are also supposed to participate in the spreading of misfolded proteins among cells in neurodegenerative diseases [37].”
BackgroundThe anesthetic sevoflurane induces tau trafficking from neurons to microglia
Dong, Y., Liang, F., Huang, L., Fang, F., Yang, G., Tanzi, R. E., Zhang, Y., Quan, Q., & Xie, Z. (2021) · Communications Biology · doi:10.1038/s42003-021-02047-8 · Cited by 58 · see citing works
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“The findings underscore the significant role of EVs in facilitating the intercellular transfer of disease-associated factors, contributing to the pathological progression observed in AD [88, 89].”
BackgroundCirculating markers of ageing and allostatic load: A slow train coming
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Exosomes in Parkinson’s Disease: Current Perspectives and Future Challenges
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Role of Extracellular Vesicles in Amyotrophic Lateral Sclerosis
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The path to biomarker-based diagnostic criteria for the spectrum of neurodegenerative diseases
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“…be studied intensively in the nervous system, both as a novel means of intercellular communication and as a pathogenic mechanism in neurodegeneration (Chivet et al., 2013; Costanzo and Zurzolo, 2013; Schneider and Simons, 2013; Rajendran et al., 2014; Tsilioni et al., 2014; Coleman and Hill, 2015).”
BackgroundExtracellular vesicles as vital players in drug delivery: a focus on clinical disease treatment
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“EVs have been identified as putative biomarkers for several neurological disorders, including Alzheimer’s disease, Parkinson’s disease and multiple sclerosis [29,30,40,41].”
BackgroundImpaired activation of ALS monocytes by exosomes
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Extracellular vesicles in neurodegenerative diseases: A systematic review
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Intercellular Communication in the Nervous System goes Viral
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“Although controversial, the involvement of extracellular vesicles in the inter-neuronal spread of misfolded proteins for has been proposed [37, 96].”
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“The role of extracellular vesicles has been related to cell signaling and removal of misfolded molecules [138].”
Background
- Authors
- Coleman, B. M., & Hill, A. F.
- Affiliations
- The University of Melbourne (AU)
- Corresponding author
- Hill, Andrew F.
- ORCID
- Hill, Andrew F.
- Venue
- Seminars in Cell & Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 40
- Pages
- 89-96
- ISSN
- 1084-9521 (ISSN-L)
- OpenAlex
- W1988327113
- Cited by
- 208
- References
- 0
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 13 · 2023: 14 · 2022: 17 · 2021: 25 · 2020: 33 · 2019: 16 · 2018: 17 · 2017: 21 · 2016: 29 · 2015: 8
- FWCI
- 2.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Seminars in Cell and Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Victoria University Research Repository (Victoria University) (submittedVersion)
- Funders
- National Health and Medical Research Council (628946)
- Australian Research Council Future Fellow (FT100100560)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- extracellular vesicles, exosomes, prions, misfolded proteins, neurodegenerative diseases, Creutzfeldt-Jakob disease, bovine spongiform encephalopathy, amyloid precursor protein, Alzheimer's disease, microRNA, mRNA, cell-to-cell communication, prion-like proteins, biomarkers, cerebrospinal fluid, serum, urine
- MeSH terms
- Extracellular Vesicles, Animals, Humans, Prions, Protein Folding, Neurodegenerative Diseases, MicroRNAs
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