Cytosine β-D-arabinofuranoside used as a paradigm modifier to increase production of tau aggregates in a cellular model of tauopathy

Li Wen Ko, Jayanarayan G. Kulathingal, Shu Hui C. Yen

Research output: Contribution to journalArticle

3 Scopus citations

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 languageEnglish (US)
Pages (from-to)823-832
Number of pages10
JournalNeurochemical Research
Volume32
Issue number4-5
DOIs
StatePublished - Apr 1 2007

Keywords

  • Alzheimer's disease
  • Cellular model
  • Neurofibrillary degeneration
  • Tau
  • Tauopathy

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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