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Microtubule-binding drugs offset tau sequestration by stabilizing microtubules and reversing fast axonal transport deficits in a tauopathy model


Year of Publication:
Contact PI Name:
John Q. Trojanowski
Contact PI Affiliation:
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Bin Zhang, Arpita Maiti, Sharon Shively, Fara Lakhani, Gaye McDonald-Jones, Jennifer Bruce, Edward B. Lee, Sharon X. Xie, Sonali Joyce, Chi Li, Philip M. Toleikis, Virginia M-Y. Lee
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
Oxford Foundation
Marian S. Ware Alzheimer Program
Angiotech Pharmaceuticals
Applied Neurotechnology Inc.
Study Goal and Principal Findings:

They tested the hypothesis that microtubule (MT)-binding drugs could be therapeutically beneficial in tauopathies by functionally substituting for the MT-binding protein tau, which is sequestered into inclusions of human tauopathies and transgenic mouse models thereof. Transgenic mice were treated for 12 weeks with weekly i.p. injections of 10 or 25 mg/m2 paclitaxel (Paxceed). Both doses restored fast axonal transport in spinal axons, wherein MT numbers and stable (detyrosinated) tubulins were increased, compared with sham treatment, and only Paxceed ameliorated motor impairments in tau transgenic mice. Thus, MT-stabilizing drugs could have therapeutic potential for treating neurodegenerative tauopathies by offsetting losses of tau function that result from the sequestration of this MT-stabilizing protein into filamentous inclusions.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Therapeutic Target:
Tubulin (Microtubules)

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest


Outcome Measured
Outcome Parameters
Motor Function
Tail Suspension Test
Tau Pathology
Fast Axonal Transport (FAT)
Neurofilament M (NF-M)
beta Tubulin
alpha Tubulin
Detyrosinated Tubulin (Glu-Tub)
Acetylated Tubulin
Tyrosinated Tubulin (Tyr-Tub)
Tau Protein
Electron Microscopy
Microtubule Density
Dystrophic Axons