The proton-pump inhibitor lansoprazole enhances amyloid beta production

PLoS One. 2013;8(3):e58837. doi: 10.1371/journal.pone.0058837. Epub 2013 Mar 8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles / pharmacology*
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / biosynthesis*
  • Amyloid beta-Peptides / genetics
  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Disease Models, Animal
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Humans
  • Lansoprazole
  • Mice
  • Mice, Knockout
  • Proton Pump Inhibitors*

Substances

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Amyloid beta-Peptides
  • Enzyme Inhibitors
  • Proton Pump Inhibitors
  • Lansoprazole

Grant support

The present work has been supported by the Spanish Ministerio de Ciencia e Innovación (PSE-010000-2009-1; BIO2010-22073) and by the own fund of each institute, and the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.