Journal article
Reevaluating tau reduction as a therapeutic approach for tauopathies: Insights and perspectives
Cytoskeleton (Hoboken, N.J.)
11 Oct 2023
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Abstract Tau, one of the most abundant microtubule‐associated protein in neurons plays a role in regulating microtubule dynamics in axons, as well as shaping the overall morphology of the axon. Recent studies challenge the traditional view of tau as a microtubule stabilizer and shed new light on the complexity of its role in regulating various properties of the microtubule. While reducing tau levels shows therapeutic promise for early tauopathies, efficacy wanes in later stages due to resilient toxic tau aggregates and neurofibrillary tangles. Notably, tauopathies involve factors beyond toxic tau alone, necessitating a broader therapeutic approach. Overexpression of human tau in mouse models, although useful for answering some questions, may not accurately reflect disease mechanisms in patients with tauopathies. Furthermore, the interplay between tau and MAP6, another microtubule‐associated protein, adds complexity to tau's regulation of microtubule dynamics. Tau promotes the formation and elongation of labile microtubule domains, vital for cellular processes, while MAP6 stabilizes microtubules. A delicate balance between these proteins is important for neuronal function. Therefore, tau reduction therapies require a comprehensive understanding of disease progression, considering functional tau loss, toxic aggregates, and microtubule dynamics. Stage‐dependent application and potential unintended consequences must be carefully evaluated. Restoring microtubule dynamics in late‐stage tauopathies may necessitate alternative strategies. This knowledge is valuable for developing effective and safe treatments for tauopathies.
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Details
- Title
- Reevaluating tau reduction as a therapeutic approach for tauopathies: Insights and perspectives
- Creators
- Xiaohuan Sun - Drexel UniversityVictor C. Ogbolu - Drexel UniversityPeter W. Baas - Drexel UniversityLiang Qiang - Drexel University
- Publication Details
- Cytoskeleton (Hoboken, N.J.)
- Publisher
- Wiley
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; Pharmacology and Physiology
- Web of Science ID
- WOS:001082367000001
- Scopus ID
- 2-s2.0-85173647604
- Other Identifier
- 991021446359604721
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- Cell Biology