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Prion-like Properties of Tau Protein: The Importance of Extracellular Tau as a Therapeutic Target
Open accessAbstract
Work over the past 4 years indicates that multiple proteins associated with neurodegenerative diseases, especially Tau and α-synuclein, can propagate aggregates between cells in a prion-like manner. This means that once an aggregate is formed it can escape the cell of origin, contact a connected cell, enter the cell, and induce further aggregation via templated conformational change. The prion model predicts a key role for extracellular protein aggregates in mediating progression of disease. This suggests new therapeutic approaches based on blocking neuronal uptake of protein aggregates and promoting their clearance. This will likely include therapeutic antibodies or small molecules, both of which can be developed and optimized in vitro prior to preclinical studies.
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“Intriguingly, over the past decade, HSPGs have been revealed as essential players in the cellular uptake of Tau46–48.”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [48]
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“Previous work showed that HSPGs are largely responsible for neuronal Tau uptake46–48,57.”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [48]
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Citations
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Cited by
Sorted by citations
Tau in physiology and pathology
Wang, Y., & Mandelkow, E. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.1 · Cited by 2,251
Proteopathic tau seeding predicts tauopathy in vivo
Holmes, B. B., Furman, J. L., Mahan, T. E., Yamasaki, T. R., Mirbaha, H., Eades, W. C., Belaygorod, L., Cairns, N. J., Holtzman, D. M., & Diamond, M. I. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1411649111 · Cited by 696
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Amyloid-β and tau complexity — towards improved biomarkers and targeted therapies
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Metadata
- Authors
- Holmes, B. B., & Diamond, M. I.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Diamond, Marc I.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 289
- Issue
- 29
- Pages
- 19855-19861
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC4106306
- OpenAlex
- W2068440450
- Cited by
- 202
- References
- 101
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 10 · 2023: 14 · 2022: 13 · 2021: 10 · 2020: 28 · 2019: 22 · 2018: 27 · 2017: 15 · 2016: 18 · 2015: 17 · 2014: 10
- FWCI
- 2.34
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1R01NS071835-01, 5 F31 NS079039-03)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- tau protein, prion-like propagation, alpha-synuclein, neurodegenerative diseases, therapeutic antibodies, small molecule drugs, aggregate clearance
- MeSH terms
- Alzheimer Disease, Animals, Cell Membrane, Humans, Prions, Protein Conformation, Vaccines, Amyloid beta-Peptides, tau Proteins, Heparan Sulfate Proteoglycans, Protein Transport, Tauopathies, alpha-Synuclein, Protein Multimerization
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