Nature Communications (Apr 2019)
Felodipine induces autophagy in mouse brains with pharmacokinetics amenable to repurposing
- Farah H. Siddiqi,
- Fiona M. Menzies,
- Ana Lopez,
- Eleanna Stamatakou,
- Cansu Karabiyik,
- Rodrigo Ureshino,
- Thomas Ricketts,
- Maria Jimenez-Sanchez,
- Miguel Angel Esteban,
- Liangxue Lai,
- Micky D. Tortorella,
- Zhiwei Luo,
- Hao Liu,
- Emmanouil Metzakopian,
- Hugo J. R. Fernandes,
- Andrew Bassett,
- Eric Karran,
- Bruce L. Miller,
- Angeleen Fleming,
- David C. Rubinsztein
Affiliations
- Farah H. Siddiqi
- Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge
- Fiona M. Menzies
- Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge
- Ana Lopez
- Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge
- Eleanna Stamatakou
- Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge
- Cansu Karabiyik
- Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge
- Rodrigo Ureshino
- Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge
- Thomas Ricketts
- Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge
- Maria Jimenez-Sanchez
- Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge
- Miguel Angel Esteban
- Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
- Liangxue Lai
- Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
- Micky D. Tortorella
- Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
- Zhiwei Luo
- Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
- Hao Liu
- Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
- Emmanouil Metzakopian
- UK Dementia Research Institute, Department of Clinical Neurosciences, University of Cambridge
- Hugo J. R. Fernandes
- UK Dementia Research Institute, Department of Clinical Neurosciences, University of Cambridge
- Andrew Bassett
- Wellcome Sanger Institute, Wellcome Genome Campus
- Eric Karran
- AbbVie Inc., Foundational Neuroscience Center
- Bruce L. Miller
- Memory and Aging Center, Department of Neurology, University of California
- Angeleen Fleming
- Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge
- David C. Rubinsztein
- Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge
- DOI
- https://doi.org/10.1038/s41467-019-09494-2
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 14
Abstract
A key challenge is to find/re-purpose approved drugs that could be used in humans to induce autophagy-associated clearance of neurodegenerative proteins. Here, authors demonstrate that felodipine, an anti-hypertensive drug, can induce autophagy and clear a variety of aggregated neurodegenerative disease-associated proteins in mouse brains at plasma concentrations similar to those that would be seen in humans taking the drug.
