Molecular Modulation of Human α7 Nicotinic Receptor by Amyloid-β Peptides

Frontiers in Cellular Neuroscience
Matías LasalaCecilia Bouzat

Abstract

Amyloid β peptide (Aβ) is a key player in the development of Alzheimer's disease (AD). It is the primary component of senile plaques in AD patients and is also found in soluble forms. Cholinergic activity mediated by α7 nicotinic receptors has been shown to be affected by Aβ soluble forms. To shed light into the molecular mechanism of this effect, we explored the direct actions of oligomeric Aβ1-40 and Aβ1-42 on human α7 by fluorescence spectroscopy and single-channel recordings. Fluorescence measurements using the conformational sensitive probe crystal violet (CrV) revealed that in the presence of Aβ α7 undergoes concentration-dependent conformational changes. Exposure of α7 to 100 pM Aβ changes CrV KD towards that of the desensitized state. However, α7 is still reactive to high carbamylcholine (Carb) concentrations. These observations are compatible with the induction of active/desensitized states as well as of a novel conformational state in the presence of both Aβ and Carb. At 100 nM Aβ, α7 adopts a resting-state-like structure which does not respond to Carb, suggesting stabilization of α7 in a blocked state. In real time, we found that Aβ is capable of eliciting α7 channel activity either in the absence or presence of the ...Continue Reading

References

Mar 22, 1997·Proceedings. Biological Sciences·F QinF Sachs
Mar 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·Q LiuD K Berg
May 2, 2002·The Journal of Biological Chemistry·Kelly T DineleyJ David Sweatt
Jun 18, 2004·Journal of Alzheimer's Disease : JAD·Valentina EcheverriaA Claudio Cuello
Jun 29, 2004·Biochemical and Biophysical Research Communications·L Michel Espinoza-Fonseca
Nov 13, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Pascale N LacorWilliam L Klein
Dec 21, 2004·Nature Neuroscience·James P ClearyKaren H Ashe
Apr 29, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Raymond S HurstStephen P Arneric
Jul 14, 2005·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Gal BitanDavid B Teplow
Jun 16, 2007·Frontiers in Bioscience : a Journal and Virtual Library·Kelly T Dineley
Jul 13, 2007·The Journal of Pharmacology and Experimental Therapeutics·Daniel B TimmermannGunnar M Olsen
Aug 21, 2007·Biochemical Pharmacology·Daniel Bertrand, Murali Gopalakrishnan
May 31, 2008·The Journal of Biological Chemistry·Gaspar A Fernández NievasSilvia S Antollini
Aug 1, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Cecilia BouzatSteven M Sine
Mar 19, 2009·Pharmacological Reviews·Steven D BuckinghamDavid B Sattelle
Aug 28, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Maria Laura GiuffridaAgata Copani
Sep 18, 2010·Journal of Alzheimer's Disease : JAD·Mordhwaj S Parihar, Gregory J Brewer
Mar 26, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jaskiran K GillNeil S Millar
Apr 8, 2011·Annals of Neurology·Daniela PuzzoOttavio Arancio
Jul 19, 2011·Biochemical Pharmacology·H Rheinallt ParriKelly T Dineley
Oct 1, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Corrie J B daCostaSteven M Sine
Jan 5, 2012·Journal of Alzheimer's Disease : JAD·Alexander Navarrete SantosHarald Hampel
Nov 28, 2012·Brain Research Bulletin·Balázs LendvaiZsolt Némethy
Dec 13, 2012·Expert Opinion on Therapeutic Targets·Tanya L Wallace, Daniel Bertrand
Jan 29, 2013·Acta Neuropathologica·Andrew D WattKevin J Barnham
Nov 5, 2013·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Nadine KabbaniDavid J Adams
Dec 3, 2013·Alzheimer's Research & Therapy·Eric Y Hayden, David B Teplow

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Citations

Nov 30, 2019·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Dimitri HefterMartin Korte
Aug 1, 2020·Frontiers in Cell and Developmental Biology·Elena V MitroshinaMaria V Vedunova
Sep 11, 2020·Journal of Clinical Medicine·Katrin RichterAndreas Hecker
Apr 18, 2021·Cellular and Molecular Life Sciences : CMLS·Daniela AnniAnna Fejtova

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Methods Mentioned

BETA
transfections
transfection
fluorescence spectroscopy

Software Mentioned

Graphpad PRISM
QuB
Origin

Related Concepts

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