The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
A nucleated assembly mechanism of Alzheimer paired helical filaments
Abstract
Alzheimer’s disease is characterized by two types of fibrous aggregates in the affected brains, the amyloid fibers (consisting of the Aβ-peptide, generating the amyloid plaques), and paired helical filaments (PHFs; made up of tau protein, forming the neurofibrillary tangles). Hence, tau protein, a highly soluble protein that normally stabilizes microtubules, becomes aggregated into insoluble fibers that obstruct the cytoplasm of neurons and cause a loss of microtubule stability. We have developed recently a rapid assay for monitoring PHF assembly and show here that PHFs arise from a nucleated assembly mechanism. The PHF nucleus comprises about 8–14 tau monomers. A prerequisite for nucleation is the dimerization of tau because tau dimers act as effective building blocks. PHF assembly can be seeded by preformed filaments (made either in vitro or isolated from Alzheimer brain tissue). These results suggest that dimerization and nucleation are the rate-limiting steps for PHF formation in vivo .
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“In order to undergo a liquid-to-solid phase transition and aggregate into tangles, the presence of polyanionic factors such as heparin and RNA or a specific yet unknown phosphorylation pattern are critical23, 24.”
From Liquid–liquid phase separation of the microtubule-binding repeats of the Alzheimer-related protein Tau (2017) · cites this paper as [24]
Citations
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Propagation of Tau Misfolding from the Outside to the Inside of a Cell
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Self-citation
Metadata
- Authors
- Friedhoff, P., von Bergen, M., Mandelkow, E.-M., Davies, P., & Mandelkow, E.
- Affiliations
- Max-Planck-Unit for Structural Molecular Biology, Notkestrasse 85, D-22607 Hamburg, Germany; and Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1998-12-22
- Volume
- 95
- Issue
- 26
- Pages
- 15712-15717
- ISSN
- 0027-8424
- 1091-6490
- Cited by
- 314
- References
- 6
- Language
- en
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- Friedhoff, P., von Bergen, M., Mandelkow, E.-M., Davies, P., & Mandelkow, E. (1998). A nucleated assembly mechanism of Alzheimer paired helical filaments. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.95.26.15712
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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