S 24795 limits beta-amyloid-alpha7 nicotinic receptor interaction and reduces Alzheimer's disease-like pathologies

Biological Psychiatry
Hoau-Yan WangPhilippe Morain

Abstract

Beta-amyloid (Abeta) enables Alzheimer's disease (AD) plaque and neurofibrillary pathogenesis. Soluble Abeta promotes intraneuronal Abeta aggregates and tau phosphorylation by interacting with alpha7 nicotinic receptors (alpha7nAChRs). The current study assessed whether the novel alpha7nAChR partial agonist 2-(2-(4-bromophenyl)-2-oxoethyl)-1-methyl pyridinium (S 24795) could reduce AD-like pathologies by interfering with Abeta-alpha7nAChR interaction. We compared the in vitro effect of S 24795, memantine, galantamine, and Abeta(12-28) on Abeta(42)-alpha7nAChR interaction in rat hippocampal synaptosomes. We further evaluated the effect of S 24795 on Abeta(42)-induced tau phosphorylation with rat hippocampal synaptosomes in vitro. Effects of S 24795 on Abeta(42) immunostaining, Abeta(42)-alpha7nAChR interaction, and/or Abeta(42)-mediated reduction of calcium (Ca(2+)) influx through alpha7nAChR and N-methyl-d-aspartate receptor (NMDAR) were assessed in Abeta(42)-incubated organotypic brain slices and intracerebroventricularly (ICV) Abeta(42)-injected mouse brain. Preincubation with S 24795 in vitro reduces Abeta(42)-alpha7nAChR interaction and Abeta(42)-induced tau phosphorylation. In organotypic brain slice cultures and in an ICV...Continue Reading

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Citations

Jul 28, 2012·International Journal of Molecular Sciences·Li Na ZhaoLock Yue Chew
Feb 26, 2011·International Journal of Alzheimer's Disease·Amany Mohamed, Elena Posse de Chaves
Jan 22, 2011·International Journal of Alzheimer's Disease·Jin WuKenji Hashimoto
Nov 18, 2014·Expert Opinion on Therapeutic Targets·Kenji Hashimoto
Apr 14, 2019·British Journal of Pharmacology·Erika CeconRalf Jockers
Oct 1, 2015·Pharmacological Reviews·Daniel BertrandDiana Donnelly-Roberts
Sep 3, 2020·International Journal of Molecular Sciences·Evgeny P BarykinAlexander A Makarov
Jan 14, 2021·Neuroscience and Biobehavioral Reviews·Vanessa Lissek, Boris Suchan
Jan 19, 2021·Journal of Alzheimer's Disease : JAD·Kejing LaoXingchun Gou
Jun 19, 2015·The Journal of Physical Chemistry. B·Li Na ZhaoYuguang Mu
Jul 19, 2011·Biochemical Pharmacology·H Rheinallt ParriKelly T Dineley

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