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NX210c 肽促进小鼠中枢神经系统中谷氨酸能受体介导的突触传递和信号转导。

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

机构信息

Axoltis Pharma, 60 Avenue Rockefeller, 69008 Lyon, France.

Neuro-Sys, 410 Chemin Départemental 60, 13120 Gardanne, France.

出版信息

Int J Mol Sci. 2022 Aug 9;23(16):8867. doi: 10.3390/ijms23168867.

DOI:10.3390/ijms23168867
PMID:36012124
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9408760/
Abstract

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.

摘要

NX210c 是一种源自 subcommissural 器官-蛛丝蛋白的疾病修饰十二肽，目前处于临床前和临床开发阶段，用于治疗神经紊乱。在这里，我们使用全细胞膜片钳记录技术证明，NX210c 增加了大脑中 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体 (AMPAR) 和含 GluN2A 的 N-甲基-D-天冬氨酸受体 (GluN2A-NMDA 受体) 介导的兴奋性突触后电流。因此，在存在 NX210c 的情况下，使用细胞外场兴奋性突触后电位记录显示在两个不同的神经元回路中增强了突触传递。此外，NX210c 对突触传递和 GluN2A-NMDA 受体驱动的信号的调节恢复了长期用 NMDA 受体拮抗剂苯环利定治疗的小鼠的记忆。总的来说，通过促进谷氨酸能受体相关的神经传递和信号，NX210c 为患有中枢神经系统疾病、损伤和伴有严重突触功能障碍的患者提供了一种创新的治疗机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/806b/9408760/a6e04fbc31f5/ijms-23-08867-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/806b/9408760/73b90e82cd2a/ijms-23-08867-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/806b/9408760/d6ab924c935d/ijms-23-08867-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/806b/9408760/b9224939917c/ijms-23-08867-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/806b/9408760/a6e04fbc31f5/ijms-23-08867-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/806b/9408760/73b90e82cd2a/ijms-23-08867-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/806b/9408760/d6ab924c935d/ijms-23-08867-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/806b/9408760/b9224939917c/ijms-23-08867-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/806b/9408760/a6e04fbc31f5/ijms-23-08867-sch001.jpg

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