Cytosine beta-D-arabinofuranoside used as a paradigm modifier to increase production of tau aggregates in a cellular model of tauopathy.
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.
Ko
Li-Wen
LW
Department of Neuroscience, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, FL 32224, USA. ko.li-wen@mayo.edu
Kulathingal
Jayanarayan G
JG
Yen
Shu-Hui C
SH
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D006801:Humans; D007700:Kinetics; D009447:Neuroblastoma / Q000473:pathology; D014404:Tubulin / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; D014404:Tubulin; D016875:tau Proteins; D003561:Cytarabine