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NX210c Peptide Promotes Glutamatergic Receptor-Mediated Synaptic Transmission and Signaling in the Mouse Central Nervous System

NX210c is a disease-modifying dodecapeptide derived from the subcommissural organ-spondin that is under preclinical and clinical development for the treatment of neurological disorders. Here, using whole-cell patch-clamp recordings, we demonstrate that NX210c increased α-amino-3-hydroxy-5-methyl-4-i...

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Autores principales: Lemarchant, Sighild, Sourioux, Mélissa, Le Douce, Juliette, Henriques, Alexandre, Callizot, Noëlle, Hugues, Sandrine, Farinelli, Mélissa, Godfrin, Yann
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9408760/
https://www.ncbi.nlm.nih.gov/pubmed/36012124
http://dx.doi.org/10.3390/ijms23168867
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author Lemarchant, Sighild
Sourioux, Mélissa
Le Douce, Juliette
Henriques, Alexandre
Callizot, Noëlle
Hugues, Sandrine
Farinelli, Mélissa
Godfrin, Yann
author_facet Lemarchant, Sighild
Sourioux, Mélissa
Le Douce, Juliette
Henriques, Alexandre
Callizot, Noëlle
Hugues, Sandrine
Farinelli, Mélissa
Godfrin, Yann
author_sort Lemarchant, Sighild
collection PubMed
description NX210c is a disease-modifying dodecapeptide derived from the subcommissural organ-spondin that is under preclinical and clinical development for the treatment of neurological disorders. Here, using whole-cell patch-clamp recordings, we demonstrate that NX210c increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)- and GluN2A-containing N-methyl-D-aspartate receptor (GluN2A-NMDAR)-mediated excitatory postsynaptic currents in the brain. Accordingly, using extracellular field excitatory postsynaptic potential recordings, an enhancement of synaptic transmission was shown in the presence of NX210c in two different neuronal circuits. Furthermore, the modulation of synaptic transmission and GluN2A-NMDAR-driven signaling by NX210c restored memory in mice chronically treated with the NMDAR antagonist phencyclidine. Overall, by promoting glutamatergic receptor-related neurotransmission and signaling, NX210c represents an innovative therapeutic opportunity for patients suffering from CNS disorders, injuries, and states with crippling synaptic dysfunctions.
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spelling pubmed-94087602022-08-26 NX210c Peptide Promotes Glutamatergic Receptor-Mediated Synaptic Transmission and Signaling in the Mouse Central Nervous System Lemarchant, Sighild Sourioux, Mélissa Le Douce, Juliette Henriques, Alexandre Callizot, Noëlle Hugues, Sandrine Farinelli, Mélissa Godfrin, Yann Int J Mol Sci Article NX210c is a disease-modifying dodecapeptide derived from the subcommissural organ-spondin that is under preclinical and clinical development for the treatment of neurological disorders. Here, using whole-cell patch-clamp recordings, we demonstrate that NX210c increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)- and GluN2A-containing N-methyl-D-aspartate receptor (GluN2A-NMDAR)-mediated excitatory postsynaptic currents in the brain. Accordingly, using extracellular field excitatory postsynaptic potential recordings, an enhancement of synaptic transmission was shown in the presence of NX210c in two different neuronal circuits. Furthermore, the modulation of synaptic transmission and GluN2A-NMDAR-driven signaling by NX210c restored memory in mice chronically treated with the NMDAR antagonist phencyclidine. Overall, by promoting glutamatergic receptor-related neurotransmission and signaling, NX210c represents an innovative therapeutic opportunity for patients suffering from CNS disorders, injuries, and states with crippling synaptic dysfunctions. MDPI 2022-08-09 /pmc/articles/PMC9408760/ /pubmed/36012124 http://dx.doi.org/10.3390/ijms23168867 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lemarchant, Sighild
Sourioux, Mélissa
Le Douce, Juliette
Henriques, Alexandre
Callizot, Noëlle
Hugues, Sandrine
Farinelli, Mélissa
Godfrin, Yann
NX210c Peptide Promotes Glutamatergic Receptor-Mediated Synaptic Transmission and Signaling in the Mouse Central Nervous System
title NX210c Peptide Promotes Glutamatergic Receptor-Mediated Synaptic Transmission and Signaling in the Mouse Central Nervous System
title_full NX210c Peptide Promotes Glutamatergic Receptor-Mediated Synaptic Transmission and Signaling in the Mouse Central Nervous System
title_fullStr NX210c Peptide Promotes Glutamatergic Receptor-Mediated Synaptic Transmission and Signaling in the Mouse Central Nervous System
title_full_unstemmed NX210c Peptide Promotes Glutamatergic Receptor-Mediated Synaptic Transmission and Signaling in the Mouse Central Nervous System
title_short NX210c Peptide Promotes Glutamatergic Receptor-Mediated Synaptic Transmission and Signaling in the Mouse Central Nervous System
title_sort nx210c peptide promotes glutamatergic receptor-mediated synaptic transmission and signaling in the mouse central nervous system
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9408760/
https://www.ncbi.nlm.nih.gov/pubmed/36012124
http://dx.doi.org/10.3390/ijms23168867
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