The proton-pump inhibitor lansoprazole enhances amyloid beta production.

A key event in the pathogenesis of Alzheimer's disease (AD) is the accumulation of amyloid-β (Aβ) species in the brain, derived from the sequential cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. Based on a systems biology study to repurpose drugs for AD, we explore the...

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Autores principales:	Nahuai Badiola, Victor Alcalde, Albert Pujol, Lisa-Marie Münter, Gerd Multhaup, Alberto Lleó, Mireia Coma, Montserrat Soler-López, Patrick Aloy
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aaaf0f44a49646f28a9a25d4605314d4
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spelling	oai:doaj.org-article:aaaf0f44a49646f28a9a25d4605314d42021-11-18T07:54:07ZThe proton-pump inhibitor lansoprazole enhances amyloid beta production.1932-620310.1371/journal.pone.0058837https://doaj.org/article/aaaf0f44a49646f28a9a25d4605314d42013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23520537/?tool=EBIhttps://doaj.org/toc/1932-6203A key event in the pathogenesis of Alzheimer's disease (AD) is the accumulation of amyloid-β (Aβ) species in the brain, derived from the sequential cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. Based on a systems biology study to repurpose drugs for AD, we explore the effect of lansoprazole, and other proton-pump inhibitors (PPIs), on Aβ production in AD cellular and animal models. We found that lansoprazole enhances Aβ37, Aβ40 and Aβ42 production and lowers Aβ38 levels on amyloid cell models. Interestingly, acute lansoprazole treatment in wild type and AD transgenic mice promoted higher Aβ40 levels in brain, indicating that lansoprazole may also exacerbate Aβ production in vivo. Overall, our data presents for the first time that PPIs can affect amyloid metabolism, both in vitro and in vivo.Nahuai BadiolaVictor AlcaldeAlbert PujolLisa-Marie MünterGerd MulthaupAlberto LleóMireia ComaMontserrat Soler-LópezPatrick AloyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e58837 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nahuai Badiola Victor Alcalde Albert Pujol Lisa-Marie Münter Gerd Multhaup Alberto Lleó Mireia Coma Montserrat Soler-López Patrick Aloy The proton-pump inhibitor lansoprazole enhances amyloid beta production.
description	A key event in the pathogenesis of Alzheimer's disease (AD) is the accumulation of amyloid-β (Aβ) species in the brain, derived from the sequential cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. Based on a systems biology study to repurpose drugs for AD, we explore the effect of lansoprazole, and other proton-pump inhibitors (PPIs), on Aβ production in AD cellular and animal models. We found that lansoprazole enhances Aβ37, Aβ40 and Aβ42 production and lowers Aβ38 levels on amyloid cell models. Interestingly, acute lansoprazole treatment in wild type and AD transgenic mice promoted higher Aβ40 levels in brain, indicating that lansoprazole may also exacerbate Aβ production in vivo. Overall, our data presents for the first time that PPIs can affect amyloid metabolism, both in vitro and in vivo.
format	article
author	Nahuai Badiola Victor Alcalde Albert Pujol Lisa-Marie Münter Gerd Multhaup Alberto Lleó Mireia Coma Montserrat Soler-López Patrick Aloy
author_facet	Nahuai Badiola Victor Alcalde Albert Pujol Lisa-Marie Münter Gerd Multhaup Alberto Lleó Mireia Coma Montserrat Soler-López Patrick Aloy
author_sort	Nahuai Badiola
title	The proton-pump inhibitor lansoprazole enhances amyloid beta production.
title_short	The proton-pump inhibitor lansoprazole enhances amyloid beta production.
title_full	The proton-pump inhibitor lansoprazole enhances amyloid beta production.
title_fullStr	The proton-pump inhibitor lansoprazole enhances amyloid beta production.
title_full_unstemmed	The proton-pump inhibitor lansoprazole enhances amyloid beta production.
title_sort	proton-pump inhibitor lansoprazole enhances amyloid beta production.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/aaaf0f44a49646f28a9a25d4605314d4
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The proton-pump inhibitor lansoprazole enhances amyloid beta production.

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