GluN3A is a glycine-binding subunit belonging to the NMDA receptor (NMDAR) family that can assemble with GluN1 subunits to form unconventional NMDARs insensitive to glutamate and activated by glycine only. The existence of such excitatory glycine receptors (eGlyRs) in the central nervous system (CNS) has long remained elusive. Recently, eGlyRs have been identified in specific brain regions, where they represent a novel neuronal signaling modality by which extracellular glycine tunes neuronal excitability, circuit function, and behavior. In this review, we summarize the emerging knowledge regarding these underappreciated receptors. The existence of eGlyRs reshapes current understanding of NMDAR diversity and of glycinergic signaling, previously thought to be primarily inhibitory. Given that GluN3A expression is concentrated in brain regions regulating emotional responses, eGlyRs are potential new targets of therapeutic interest in neuropsychiatry.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.tins.2023.05.002 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Efficacy of apheresis in antibody-negative progressive encephalomyelitis with rigidity and myoclonus.
Ther Apher Dial
January 2025
Department of Neurology, Wakayama Medical University, Wakayama, Japan.
Introduction: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is characterized by brainstem symptoms, muscle rigidity, and myoclonus. While autoantibodies to inhibitory neurons have been associated with the pathology, about 30% of cases are negative for autoantibodies. There are few reported cases of antibody-negative PERM and its clinical course and prognosis are unknown.
View Article and Find Full Text PDFImpaired Presynaptic Function Contributes Significantly to the Pathology of Glycine Receptor Autoantibodies.
Neurol Neuroimmunol Neuroinflamm
March 2025
Institute for Clinical Neurobiology, University Hospital, Julius-Maximilians-University of Würzburg, Germany.
Background And Objectives: Autoantibodies (aAbs) against glycine receptors (GlyRs) are mainly associated with the rare neurologic diseases stiff person syndrome (SPS) and progressive encephalomyelitis with rigidity and myoclonus (PERM). GlyR aAbs are also found in other neurologic diseases such as epilepsy. The aAbs bind to different GlyR α-subunits and, more rarely, also to the GlyR β-subunit.
View Article and Find Full Text PDFRepeated injections of isovaline lead to analgesic tolerance and cross-tolerance to salicylate but not to morphine in male mice.
Drug Res (Stuttg)
January 2025
Department of Physiology, School of Medicine, Arak University of Medical Sciences, Arak, Iran.
Tolerance to the antinociceptive effects of opioids is a major concern. Studies have shown that chronic use of non-steroidal anti-inflammatory (NSAIDs) causes significant tolerance and cross-tolerance to morphine. Chronic NSAIDs use can increase the risk of certain diseases, such as peptic ulcers, and exacerbate others, like heart failure.
View Article and Find Full Text PDF[Advances in inhibitory ion channel glycine receptors].
Sheng Li Xue Bao
December 2024
Department of Clinical Psychology, Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250117, China.
Glycine receptors (GlyRs) belong to the ligand-gated ion channel receptor superfamily and are widely distributed throughout the central nervous system. GlyRs are essential for maintaining visual, auditory, sensory and motor functions, and abnormalities in its structure and function can lead to various neurological disorders. This review aims to provide an extensive analysis of the structure, function and regulatory mechanisms of GlyRs, and evaluate its role in various central nervous system diseases.
View Article and Find Full Text PDFStructural insights into the activation mechanism of the human zinc-activated channel.
Nat Commun
January 2025
State Key Laboratory of Medicinal Chemical Biology and Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin, 300350, China.
The zinc-activated channel (ZAC) is an atypical mammalian cys-loop receptor (CLR) that is activated by zinc ions and protons, allowing cations to pass through. The molecular mechanism that ligands use to activate ZAC remains elusive. Here, we present three cryo-electron microscopy reconstructions of human ZAC (hZAC) under different conditions.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!