Rapamycin attenuates the progression of tau pathology in P301S tau transgenic mice.
Open accessAbstract
Altered autophagy contributes to the pathogenesis of Alzheimer's disease and other tauopathies, for which curative treatment options are still lacking. We have recently shown that trehalose reduces tau pathology in a tauopathy mouse model by stimulation of autophagy. Here, we studied the effect of the autophagy inducing drug rapamycin on the progression of tau pathology in P301S mutant tau transgenic mice. Rapamycin treatment resulted in a significant reduction in cortical tau tangles, less tau hyperphosphorylation, and lowered levels of insoluble tau in the forebrain. The favourable effect of rapamycin on tau pathology was paralleled by a qualitative reduction in astrogliosis. These effects were visible with early preventive or late treatment. We further noted an accumulation of the autophagy associated proteins p62 and LC3 in aged tangle bearing P301S mice that was lowered upon rapamycin treatment. Thus, rapamycin treatment defers the progression of tau pathology in a tauopathy animal model and autophagy stimulation may constitute a therapeutic approach for patients suffering from tauopathies.
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Rapamycin treatment inhibits both tau hyperphosphorylation and the development of status epilepticus and chronic epilepsy in models of pharmacological seizure induction, temporal lobe epilepsy, and post-traumatic epilepsy.
“Rapamycin treatment inhibits both tau hyperphosphorylation (Liu et al., 2013; Ozcelik et al., 2013; Tramutola et al., 2017) and the development of status epilepticus and chronic epilepsy in models of pharmacological seizure induction (Zeng et al., 2008; Huang et al., 2010), TLE (Drion et al., 2016), and PTE (Guo et al., 2013; Butler et al., 2015).”
From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Ozcelik et al., 2013
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- Authors
- Ozcelik, S., Fraser, G., Castets, P., Schaeffer, V., Skachokova, Z., Breu, K., Clavaguera, F., Sinnreich, M., Kappos, L., Goedert, M., Tolnay, M., & Winkler, D. T.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- University Hospital of Basel (CH)
- Corresponding author
- Winkler, David Theo
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-05-07
- Volume
- 8
- Issue
- 5
- Pages
- e62459
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3646815
- OpenAlex
- W1989723790
- Cited by
- 226
- References
- 38
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 9 · 2023: 15 · 2022: 27 · 2021: 26 · 2020: 31 · 2019: 17 · 2018: 17 · 2017: 17 · 2016: 18 · 2015: 17 · 2014: 7 · 2013: 2
- FWCI
- 10.42
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- National Science Foundation
- University of Pennsylvania
- Velux Stiftung
- Parkinson's UK (K-1012)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (135214, 123812, 310030)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- rapamycin, tau pathology, P301S tau transgenic mice, tauopathy, Alzheimer's disease, autophagy, tau hyperphosphorylation, tau tangles, astrocyte activation, p62, LC3, trehalose, neuroprotection
- MeSH terms
- Animals, Astrocytes, Humans, Mice, Transgenic, Phosphorylation, Solubility, Time Factors, tau Proteins, Disease Progression, Sirolimus, Tauopathies, Mice
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