Microtubule-binding drugs offset tau sequestration by stabilizing microtubules and reversing fast axonal transport deficits in a tauopathy model
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We 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/m 2 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.
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The data presented here provide further evidence that therapeutic approaches alternative to mitigating tau phosphorylation (such as improved microtubule stability) may be productive.
“the data presented here provide further evidence that such approaches may be productive”
From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [354]
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- Authors
- Zhang, B., Maiti, A., Shively, S., Lakhani, F., McDonald-Jones, G., Bruce, J., Lee, E. B., Xie, S. X., Joyce, S., Li, C., Toleikis, P. M., Lee, V. M.-Y., & Trojanowski, J. Q.
- Affiliations
- Surgical Specialties (Canada) (CA)
- Corresponding author
- Trojanowski, John Q.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2004-12-22
- Volume
- 102
- Issue
- 1
- Pages
- 227-231
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC544048
- OpenAlex
- W2043583138
- Cited by
- 413
- References
- 4
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 17 · 2023: 5 · 2022: 14 · 2021: 12 · 2020: 19 · 2019: 14 · 2018: 13 · 2017: 28 · 2016: 27 · 2015: 21 · 2014: 33 · 2013: 26 · 2012: 27
- FWCI
- 10.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- National Institutes of Health
- National Institute on Aging (P01AG014382, AG 17486, AG 14382, P01AG017586)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- tauopathy, paclitaxel, microtubule stabilization, fast axonal transport, tau inclusions, spinal motoneurons, motor impairment, neurodegeneration, tau transgenic mice
- MeSH terms
- Animals, Antineoplastic Agents, Phytogenic, Axons, Mice, Transgenic, Microtubules, Spinal Cord, tau Proteins, Paclitaxel, Mice
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