The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Assembly of microtubule-associated protein tau into Alzheimer-like filaments induced by sulphated glycosaminoglycans
Abstract
The paired helical filament (PHF) is the major component of the neurofibrillary deposits that form a defining neuropathological characteristic of Alzheimer's disease. PHFs are composed of microtubule-associated protein tau, in a hyperphosphorylated state. Hyperphosphorylation of tau results in its inability to bind to microtubules and is believed to precede PHF assembly. However, it is unclear whether hyperphosphorylation of tau is either necessary or sufficient for PHF formation. Here we show that non-phosphorylated recombinant tau isoforms with three microtubule-binding repeats form paired helical-like filaments under physiological conditions in vitro, when incubated with sulphated glycosaminoglycans such as heparin or heparan sulphate. Furthermore, heparin prevents tau from binding to microtubules and promotes microtubule disassembly. Finally, we show that heparan sulphate and hyperphosphorylated tau coexist in nerve cells of the Alzheimer's disease brain at the earliest known stages of neurofibrillary pathology. These findings, with previous studies which show that heparin stimulates tau phosphorylation by a number of protein kinases, indicate that sulphated glycosaminoglycans may be a key factor in the formation of the neurofibrillary lesions of Alzheimer's disease.
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“Tau aggregation is promoted by proteoglycans [186], which are present in tangles, and are involved in the prion-like spread of tau pathology [187].”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [186]
In the citing paper
“that this molecule can be used as an in vitro inducer of aggregation38”
From Tau Internalization is Regulated by 6-O Sulfation on Heparan Sulfate Proteoglycans (HSPGs) (2018) · cites this paper as [38]
In the citing paper
“it has been known for years that tau can bind heparin”
From Tau Internalization is Regulated by 6-O Sulfation on Heparan Sulfate Proteoglycans (HSPGs) (2018) · cites this paper as [38]
In the citing paper
“anionic experimental cofactor models have been described to promote aggregation: heparin (Goedert et al., 1996; Fichou et al., 2018) and RNA or its associated granules (Kampers et al., 1996; Zhang et al., 2017; Dinkel et al., 2015).”
From Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease (2020) · cites this paper as Goedert et al., 1996
Citations
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Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17
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The molecular pathology of Alzheimer's disease
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Self-citationTau in physiology and pathology
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Metadata
- Authors
- Goedert, M., Jakes, R., Spillantini, M. G., Hasegawa, M., Smith, M. J., & Crowther, R. A.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Venue
- Nature
- Published
- 1996-10
- Volume
- 383
- Issue
- 6600
- Pages
- 550-553
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1994282166
- Cited by
- 1,036
- References
- 32
- Citations by year
- 2026: 29 · 2025: 35 · 2024: 43 · 2023: 47 · 2022: 57 · 2021: 50 · 2020: 43 · 2019: 47 · 2018: 50 · 2017: 48 · 2016: 26 · 2015: 27 · 2014: 20 · 2013: 42 · 2012: 30
- FWCI
- 27.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tau protein, paired helical filaments, Alzheimer's disease, neurofibrillary tangles, sulfated glycosaminoglycans, heparin, heparan sulfate, tau hyperphosphorylation, microtubule binding, microtubule disassembly, tau isoforms, neurofibrillary pathology
- MeSH terms
- Alzheimer Disease, Escherichia coli, Heparin, Heparitin Sulfate, Heparan Sulfate, Hippocampus, Humans, Neurofibrils, Phosphorylation, Protein Binding, Recombinant Proteins, tau Proteins
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