Conopeptide-Functionalized Nanoparticles Selectively Antagonize Extrasynaptic N -Methyl-d-aspartate Receptors and Protect Hippocampal Neurons from Excitotoxicity In Vitro

ACS Nano
Pierluigi ValenteRoberto Fiammengo

Abstract

N-methyl-d-aspartate receptors (NMDARs) are ionotropic glutamate receptors controlling fundamental physiological processes in the central nervous system, such as learning and memory. Excessive activation of NMDARs causes excitotoxicity and results in neurodegeneration, which is observed in a number of pathological conditions. Because of their dichotomous role, therapeutic targeting of NMDAR is difficult. However, several lines of evidence suggest that excitotoxicity is predominantly linked to extrasynaptically located NMDARs. Here, we report on a nanoparticle-based strategy to inhibit extrasynaptic NMDARs exclusively and subtype selectively, while allowing synaptic NMDARs activity. We designed gold nanoparticles (AuNPs) carrying conopeptide derivatives conjugated on their poly(ethylene glycol) coating as allosteric NMDAR inhibitors and show that these nanoparticles antagonize exclusively extrasynaptic NMDAR-mediated currents in cultured hippocampal neurons. Additionally, we show that conopeptide-functionalized AuNPs are neuroprotective in an in vitro model of excitotoxicity. By using AuNPs carrying different allosteric inhibitors with distinct NMDAR subtype selectivity such as peptide conantokin-G or peptide conantokin-R, we su...Continue Reading

References

Sep 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·J M Bekkers, C F Stevens
Oct 8, 1998·FEBS Letters·T BlandlF J Castellino
Aug 23, 2000·Molecular Pharmacology·S D Donevan, R T McCabe
Nov 30, 2000·The Journal of Biological Chemistry·T BlandlF J Castellino
Apr 24, 2002·Neuron·Kenneth R Tovar, Gary L Westbrook
Dec 8, 2004·Current Medicinal Chemistry·Richard T LayerH Steve White
Mar 16, 2005·Structure·Vladan LucićWolfgang Baumeister
Jun 22, 2005·The Journal of Biological Chemistry·Elisa A Waxman, David R Lynch
Dec 16, 2005·Proceedings of the National Academy of Sciences of the United States of America·Benoît ZuberJacques Dubochet
Jun 9, 2006·Journal of Neurophysiology·Anitha B AlexKaren S Wilcox
Sep 29, 2006·Journal of Medicinal Chemistry·Xavier MontetLee Josephson
May 17, 2007·Current Drug Targets·Mary Prorok, Francis J Castellino
Aug 25, 2007·The Journal of Physiology·Alexander Z Harris, Diana L Pettit
Oct 27, 2007·The Journal of Biological Chemistry·Russell W TeichertBaldomero M Olivera
Mar 18, 2008·Nature Neuroscience·Sofia PapadiaGiles E Hardingham
May 10, 2008·Nature Reviews. Neuroscience·Paulo S Pinheiro, Christophe Mulle
May 8, 2009·Langmuir : the ACS Journal of Surfaces and Colloids·Lisa MausRoberto Fiammengo
May 4, 2010·Brain : a Journal of Neurology·Stanislava PankratovaVladimir Berezin
Sep 16, 2010·Nature Reviews. Neuroscience·Giles E Hardingham, Hilmar Bading
Feb 12, 2011·Trends in Molecular Medicine·Ted Weita LaiYu Tian Wang
Oct 15, 2011·Trends in Pharmacological Sciences·Kevin K Ogden, Stephen F Traynelis
Feb 7, 2012·Neuropharmacology·Rashna BalsaraFrancis J Castellino
May 11, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Christine M WrogeSteven Mennerick
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Aug 31, 2012·Science Translational Medicine·Elizabeth A NanceJustin Hanes
Nov 15, 2012·Nature Communications·Oksana DmytriyevaDarya Kiryushko
May 21, 2013·Nature Reviews. Neuroscience·Pierre PaolettiQiang Zhou
May 24, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kenneth R TovarGary L Westbrook
Aug 15, 2013·Nature Reviews. Neuroscience·Hilmar Bading
Feb 5, 2014·Journal of the American Chemical Society·Federica DegliangeliRoberto Fiammengo
Apr 20, 2014·Neuron·Matthew P Parsons, Lynn A Raymond
May 31, 2014·Science·Erkan Karakas, Hiro Furukawa

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Citations

Oct 1, 2020·Materials·Maurizio VillaniLivia Visai

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