Antihypertensive drug guanabenz is active in vivo against both yeast and mammalian prions.

<h4>Background</h4>Prion-based diseases are incurable transmissible neurodegenerative disorders affecting animals and humans.<h4>Methodology/principal findings</h4>Here we report the discovery of the in vivo antiprion activity of Guanabenz (GA), an agonist of alpha2-adrenergi...

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Autores principales: Déborah Tribouillard-Tanvier, Vincent Béringue, Nathalie Desban, Fabienne Gug, Stéphane Bach, Cécile Voisset, Hervé Galons, Hubert Laude, Didier Vilette, Marc Blondel
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Publicado: Public Library of Science (PLoS) 2008
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spelling oai:doaj.org-article:8eefe3241ca1455293c7d0b0209d1fe12021-11-25T06:12:46ZAntihypertensive drug guanabenz is active in vivo against both yeast and mammalian prions.1932-620310.1371/journal.pone.0001981https://doaj.org/article/8eefe3241ca1455293c7d0b0209d1fe12008-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18431471/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Prion-based diseases are incurable transmissible neurodegenerative disorders affecting animals and humans.<h4>Methodology/principal findings</h4>Here we report the discovery of the in vivo antiprion activity of Guanabenz (GA), an agonist of alpha2-adrenergic receptors routinely used in human medicine as an antihypertensive drug. We isolated GA in a screen for drugs active in vivo against two different yeast prions using a previously described yeast-based two steps assay. GA was then shown to promote ovine PrP(Sc) clearance in a cell-based assay. These effects are very specific as evidenced by the lack of activity of some GA analogues that we generated. GA antiprion activity does not involve its agonist activity on alpha2-adrenergic receptors as other chemically close anti-hypertensive agents possessing related mechanism of action were found inactive against prions. Finally, GA showed activity in a transgenic mouse-based in vivo assay for ovine prion propagation, prolonging slightly but significantly the survival of treated animals.<h4>Conclusion/significance</h4>GA thus adds to the short list of compounds active in vivo in animal models for the treatment of prion-based diseases. Because it has been administrated for many years to treat hypertension on a daily basis, without major side-effects, our results suggest that it could be evaluated in human as a potential treatment for prion-based diseases.Déborah Tribouillard-TanvierVincent BéringueNathalie DesbanFabienne GugStéphane BachCécile VoissetHervé GalonsHubert LaudeDidier ViletteMarc BlondelPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 4, p e1981 (2008)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Déborah Tribouillard-Tanvier
Vincent Béringue
Nathalie Desban
Fabienne Gug
Stéphane Bach
Cécile Voisset
Hervé Galons
Hubert Laude
Didier Vilette
Marc Blondel
Antihypertensive drug guanabenz is active in vivo against both yeast and mammalian prions.
description <h4>Background</h4>Prion-based diseases are incurable transmissible neurodegenerative disorders affecting animals and humans.<h4>Methodology/principal findings</h4>Here we report the discovery of the in vivo antiprion activity of Guanabenz (GA), an agonist of alpha2-adrenergic receptors routinely used in human medicine as an antihypertensive drug. We isolated GA in a screen for drugs active in vivo against two different yeast prions using a previously described yeast-based two steps assay. GA was then shown to promote ovine PrP(Sc) clearance in a cell-based assay. These effects are very specific as evidenced by the lack of activity of some GA analogues that we generated. GA antiprion activity does not involve its agonist activity on alpha2-adrenergic receptors as other chemically close anti-hypertensive agents possessing related mechanism of action were found inactive against prions. Finally, GA showed activity in a transgenic mouse-based in vivo assay for ovine prion propagation, prolonging slightly but significantly the survival of treated animals.<h4>Conclusion/significance</h4>GA thus adds to the short list of compounds active in vivo in animal models for the treatment of prion-based diseases. Because it has been administrated for many years to treat hypertension on a daily basis, without major side-effects, our results suggest that it could be evaluated in human as a potential treatment for prion-based diseases.
format article
author Déborah Tribouillard-Tanvier
Vincent Béringue
Nathalie Desban
Fabienne Gug
Stéphane Bach
Cécile Voisset
Hervé Galons
Hubert Laude
Didier Vilette
Marc Blondel
author_facet Déborah Tribouillard-Tanvier
Vincent Béringue
Nathalie Desban
Fabienne Gug
Stéphane Bach
Cécile Voisset
Hervé Galons
Hubert Laude
Didier Vilette
Marc Blondel
author_sort Déborah Tribouillard-Tanvier
title Antihypertensive drug guanabenz is active in vivo against both yeast and mammalian prions.
title_short Antihypertensive drug guanabenz is active in vivo against both yeast and mammalian prions.
title_full Antihypertensive drug guanabenz is active in vivo against both yeast and mammalian prions.
title_fullStr Antihypertensive drug guanabenz is active in vivo against both yeast and mammalian prions.
title_full_unstemmed Antihypertensive drug guanabenz is active in vivo against both yeast and mammalian prions.
title_sort antihypertensive drug guanabenz is active in vivo against both yeast and mammalian prions.
publisher Public Library of Science (PLoS)
publishDate 2008
url https://doaj.org/article/8eefe3241ca1455293c7d0b0209d1fe1
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