Abstract
Intraneuronal deposition of filamentous tau is a hallmark of Alzheimer's disease (AD) and related tauopathies. We developed previously a cellular model recapitulating such tau anomaly and demonstrated therein consistent production of 70-kD tau. Importantly, the 70-kD species appears to derive from tau fragments with carboxy-terminal truncation and is larger than intact tau in size, suggesting the oligomeric nature in its assembly from tau. To generate the 70-kD tau in sufficient quantity for its characterization at the molecular level, we explored and demonstrated herein that cytosine β-D- arabinofuranoside is a useful paradigm modifier to increase production of the 70-kD tau. Such oligomeric tau was enriched thereafter by immunoprecipitation to remove tau species with intact carboxy-terminus. Two-dimensional gel electrophoresis revealed that the 70-kD tau has an isoelectric point of 5.8-6.0. Future elucidation of key aggregates will provide valuable insights into the natural history of neurofibrillary degeneration and identify novel targets to develop therapeutic interventions.
Original language | English (US) |
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Pages (from-to) | 823-832 |
Number of pages | 10 |
Journal | Neurochemical Research |
Volume | 32 |
Issue number | 4-5 |
DOIs | |
State | Published - Apr 2007 |
Keywords
- Alzheimer's disease
- Cellular model
- Neurofibrillary degeneration
- Tau
- Tauopathy
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience