Ubiquitin Is a Component of Paired Helical Filaments in Alzheimer's Disease
Abstract
Paired helical filaments (PHF), which constitute a distinct type of pathological neuronal fiber, are the principal constituent of neurofibrillary tangles that occur in the brain of patients with Alzheimer's disease. Their insolubility in sodium dodecyl sulfate and urea has prevented the analysis of their subunit composition by gel electrophoresis. A monoclonal antibody (DF2) was isolated that specifically labeled PHF at both the light and electron microscopic levels. It labeled a small polypeptide (5 kilodaltons) that was shown to be ubiquitin in immunoblots of the soluble fraction of brain homogenates. To obtain direct evidence that ubiquitin is a component of PHF, PHF were treated with concentrated formic acid and digested with lysylendopeptidase; ubiquitin-derived peptides were then identified by reversed-phase high-performance liquid chromatography. Two fragments in the PHF digest were identified as derived from ubiquitin by protein sequencing. This procedure should make possible definitive identification of other PHF components.
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The ubiquitin-proteasome system is dysfunctional in AD, leading to a build-up of ubiquitinated proteins including tau.
“The ubiquitin-proteasome system is also dysfunctional in AD, leading to a build-up of ubiquitinated proteins including tau81,82.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [81]
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- Authors
- Mori, H., Kondo, J., & Ihara, Y.
- Affiliations
- Tokyo Metropolitan Institute of Gerontology (JP)
- Mitsubishi Chemical (Japan) (JP)
- Venue
- Science
- Published
- 1987-03-27
- Volume
- 235
- Issue
- 4796
- Pages
- 1641-1644
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2026263038
- Cited by
- 843
- References
- 26
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 16 · 2023: 9 · 2022: 7 · 2021: 15 · 2020: 17 · 2019: 13 · 2018: 18 · 2017: 15 · 2016: 18 · 2015: 11 · 2014: 9 · 2013: 18 · 2012: 17
- FWCI
- 53.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- ubiquitin, paired helical filaments, Alzheimer's disease, neurofibrillary tangles, protein subunit composition
- MeSH terms
- Alzheimer Disease, Amino Acid Sequence, Antibodies, Monoclonal, Chromatography, High Pressure Liquid, Cytoskeleton, Humans, Intermediate Filaments, Microscopy, Electron, Molecular Weight, Sodium Dodecyl Sulfate, Solubility, Ubiquitins, Urea
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