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

Neurochem Res. 2007 Apr-May;32(4-5):823-32. doi: 10.1007/s11064-006-9218-4. Epub 2006 Dec 6.

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 beta-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Antimetabolites, Antineoplastic / pharmacology*
  • Blotting, Western
  • Brain Neoplasms / pathology
  • Cell Division / physiology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cytarabine / pharmacology*
  • DNA Replication / drug effects
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Fluorescent Antibody Technique
  • Humans
  • Kinetics
  • Neuroblastoma / pathology
  • Tubulin / metabolism
  • tau Proteins / metabolism*

Substances

  • Antimetabolites, Antineoplastic
  • Tubulin
  • tau Proteins
  • Cytarabine