alexa Neurofibrillary degeneration can be arrested in an in vivo cellular model of human tauopathy by application of a compound which inhibits tau filament formation in vitro.


Journal of Alzheimers Disease & Parkinsonism

Author(s): Hall GF, Lee S, Yao J, Hall GF, Lee S, Yao J

Abstract Share this page

Abstract Although tau filament formation is a central event in familial tauopathies and Alzheimer's disease (AD), the cellular consequences of neurofibrillary tangle (NFT) formation are poorly understood because of the unavailability of mammalian in vivo cellular models of neurofibrillary degeneration (NFD). We have shown that human tau forms filaments and is associated with cytodegeneration when overexpressed chronically in identified neurons (ABCs) in the lamprey central nervous system (CNS). In this model, degeneration occurs according to a stereotyped sequence that closely resembles the pattern seen in tangle-bearing neurons in AD, with both tau deposition and fragmentation beginning in distal dendrites and progressing proximally over time. This sequence has been divided into four stages ranging from (1) mild beading of terminal dendrites only through (4) extensive dendritic fragmentation and loss. Here, we show that lipid-soluble, low-molecular-weight (approx 300 Da) proprietary compounds that have been demonstrated to block tau filament formation in vitro can significantly retard the progressive degeneration of ABCs that express human tau23. Bath application of one of these compounds for periods of up to 50 d after plasmid injection prevented degeneration beyond stage 2 in 90\% of all treated cells, whereas over half of control cells showed severe degeneration by this time. This provides the first in vivo experimental evidence directly supporting a causal role for tau filament formation in the pathogenesis of NFD and suggests that intensive effort toward developing therapeutic agents for AD and other NFDs targeted at blocking tau filament formation is warranted.
  • To read the full article Visit
  • Open Access
This article was published in J Mol Neurosci and referenced in Journal of Alzheimers Disease & Parkinsonism

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version