{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:17:34Z","timestamp":1785421054006,"version":"3.56.0"},"reference-count":172,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015622","name":"Romanian Ministry of Research and Innovation CNCS-UEFISCDI","doi-asserted-by":"publisher","award":["PN-III-P4-PCE-2021-1089"],"award-info":[{"award-number":["PN-III-P4-PCE-2021-1089"]}],"id":[{"id":"10.13039\/501100015622","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PN-III-P4-PCE-2021-1089"],"award-info":[{"award-number":["PN-III-P4-PCE-2021-1089"]}],"id":[{"id":"https:\/\/ror.org\/03padf885","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Strychnine-sensitive glycine receptors (GlyRs) are pentameric ligand-gated chloride channels that mediate fast inhibitory neurotransmission in the central nervous system (CNS), with high expression in the spinal cord, brainstem, cerebellum, and retina. Beyond traditional postsynaptic phasic inhibition, emerging evidence highlights the importance of extrasynaptic GlyRs\u2014expressed in both neuronal and non-neuronal cells\u2014in mediating tonic inhibition by sensing ambient glycine levels, including in the forebrain. These non-synaptic receptors display high agonist affinity, unique subunit compositions, and distinct pharmacodynamics. Notably, recent studies have begun to implicate aberrant GlyR signaling in Alzheimer\u2019s disease (AD) pathology; however, its functional role in this specific neurodegenerative context remains only poorly understood. This review synthesizes the molecular properties and functional significance of these diverse GlyR populations, emphasizing their involvement in calcium signaling, inhibitory tone, and neural circuit modulation, while critically evaluating their emerging therapeutic potential in AD.<\/jats:p>","DOI":"10.3390\/ijms27146306","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T06:49:36Z","timestamp":1784184576000},"page":"6306","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synaptic vs. Non-Synaptic Glycine Receptors: Physiological Role and Implications in Alzheimer\u2019s Disease Pathology"],"prefix":"10.3390","volume":"27","author":[{"given":"Eva","family":"Kiss","sequence":"first","affiliation":[{"name":"Department of Genetics, Cell and Molecular Biology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of T\u00e2rgu Mures, 540142 T\u00e2rgu Mures, Romania"},{"name":"Institute of Anatomy and Cell Biology, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Kirsch","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7231-4872","authenticated-orcid":false,"given":"Stefan","family":"Kins","sequence":"additional","affiliation":[{"name":"Department of Human Biology and Human Genetics, University of Kaiserslautern, 67663 Kaiserslautern, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4140-0487","authenticated-orcid":false,"given":"Jochen","family":"Kuhse","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.neuropharm.2008.07.034","article-title":"Native glycine receptor subtypes and their physiological roles","volume":"56","author":"Lynch","year":"2009","journal-title":"Neuropharmacology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1113\/JP277626","article-title":"The role of tonic glycinergic conductance in cerebellar granule cell signalling and the effect of gain-of-function mutation","volume":"597","author":"McLaughlin","year":"2019","journal-title":"J. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nrn1625","article-title":"Variations on an inhibitory theme: Phasic and tonic activation of GABAA receptors","volume":"6","author":"Farrant","year":"2005","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1111\/j.1471-4159.2006.03908.x","article-title":"Glycine receptors: Recent insights into their structural organization and functional diversity","volume":"97","author":"Betz","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1007\/s00018-022-04506-9","article-title":"Hetero-pentamerization determines mobility and conductance of Glycine receptor \u03b13 splice variants","volume":"79","author":"Lemmens","year":"2022","journal-title":"Cell Mol. Life Sci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zeilhofer, H.U., Werynska, K., Gingras, J., and Y\u00e9venes, G.E. (2021). Glycine Receptors in Spinal Nociceptive Control\u2014An Update. Biomolecules, 11.","DOI":"10.3390\/biom11060846"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Avila, A., Nguyen, L., and Rigo, J.M. (2013). Glycine receptors and brain development. Front. Cell Neurosci., 7.","DOI":"10.3389\/fncel.2013.00184"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1002\/dneu.22549","article-title":"\u03b12-glycine receptors modulate adult hippocampal neurogenesis and spatial memory","volume":"77","author":"Lin","year":"2017","journal-title":"Dev. Neurobiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4118","DOI":"10.1172\/JCI43029","article-title":"Serotonin receptor 1A-modulated phosphorylation of glycine receptor \u03b13 controls breathing in mice","volume":"120","author":"Manzke","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.heares.2016.05.004","article-title":"Loss of glycine receptors containing the \u03b13 subunit compromises auditory nerve activity, but not outer hair cell function","volume":"337","author":"Dlugaiczyk","year":"2016","journal-title":"Hear. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1111\/ejn.13489","article-title":"Deficit in acoustic signal-in-noise detection in glycine receptor \u03b13 subunit knockout mice","volume":"45","author":"Tziridis","year":"2017","journal-title":"Eur. J. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1126\/science.1094925","article-title":"GlyR \u03b13: An essential target for spinal PGE2-mediated inflammatory pain sensitization","volume":"304","author":"Harvey","year":"2004","journal-title":"Science"},{"key":"ref_13","first-page":"5242","article-title":"Mechanism of human \u03b13\u03b2 GlyR modulation in inflammatory pain and 2, 6-DTBP interaction","volume":"16","author":"Wang","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1038\/mp.2015.139","article-title":"Genetic and functional analyses demonstrate a role for abnormal glycinergic signaling in autism","volume":"21","author":"Pilorge","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chen, X., Wilson, K.A., Schaefer, N., De Hayr, L., Windsor, M., Scalais, E., van Rijckevorsel, G., Stouffs, K., Villmann, C., and O\u2019Mara, M.L. (2022). Loss, Gain and Altered Function of GlyR \u03b12 Subunit Mutations in Neurodevelopmental Disorders. Front. Mol. Neurosci., 15.","DOI":"10.3389\/fnmol.2022.886729"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1111\/j.1582-4934.2008.00357.x","article-title":"Glycinergic tonic inhibition of hippocampal neurons with depolarizing GABAergic transmission elicits histopathological signs of temporal lobe epilepsy","volume":"12","author":"Eichler","year":"2008","journal-title":"J. Cell Mol. Med."},{"key":"ref_17","first-page":"1863","article-title":"Cerebral Cortical Circuitry Formation Requires Functional Glycine Receptors","volume":"27","author":"Morelli","year":"2017","journal-title":"Cereb. Cortex"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/s41386-020-0689-9","article-title":"Reduced sedation and increased ethanol consumption in knock-in mice expressing an ethanol insensitive alpha 2 subunit of the glycine receptor","volume":"46","author":"Gallegos","year":"2021","journal-title":"Neuropsychopharmacology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1038\/s41386-022-01459-2","article-title":"Overexpression of wild type glycine alpha 1 subunit rescues ethanol sensitivity in accumbal receptors and reduces binge drinking in mice","volume":"48","author":"Araya","year":"2023","journal-title":"Neuropsychopharmacology"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"San Martin, L.S., Armijo-Weingart, L., Araya, A., Y\u00e9venes, G.E., Harvey, R.J., and Aguayo, L.G. (2021). Contribution of GlyR \u03b13 Subunits to the Sensitivity and Effect of Ethanol in the Nucleus Accumbens. Front. Mol. Neurosci., 14.","DOI":"10.3389\/fnmol.2021.756607"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Fraser, S.D., and Harvey, R.J. (2025). The emerging role of glycine receptor \u03b12 subunit defects in neurodevelopmental disorders. Front. Mol. Neurosci., 18.","DOI":"10.3389\/fnmol.2025.1550863"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"101372","DOI":"10.1016\/j.arr.2021.101372","article-title":"Neuronal excitation\/inhibition imbalance: Core element of a translational perspective on Alzheimer pathophysiology","volume":"69","author":"Busche","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7957","DOI":"10.1038\/s41467-025-62798-4","article-title":"Distinct manifestations of excitatory-inhibitory imbalance associated with amyloid-\u03b2 and tau in patients with Alzheimer\u2019s disease","volume":"16","author":"Ranasinghe","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/S0140-6736(19)33064-8","article-title":"Epilepsy in older people","volume":"395","author":"Sen","year":"2020","journal-title":"Lancet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1001\/jamaneurol.2021.3310","article-title":"Effect of Levetiracetam on Cognition in Patients With Alzheimer Disease With and Without Epileptiform Activity: A Randomized Clinical Trial","volume":"78","author":"Vossel","year":"2021","journal-title":"JAMA Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"109640","DOI":"10.1016\/j.yebeh.2024.109640","article-title":"The crosstalk between epilepsy and dementia: A systematic review and meta-analysis","volume":"152","author":"Chen","year":"2024","journal-title":"Epilepsy Behav."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9389","DOI":"10.1016\/S0021-9258(18)34082-1","article-title":"Purification by affinity chromatography of the glycine receptor of rat spinal cord","volume":"257","author":"Pfeiffer","year":"1982","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/330025b0","article-title":"Glycine vs GABA receptors","volume":"330","author":"Grenningloh","year":"1987","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/0896-6273(92)90136-2","article-title":"Primary structure and alternative splice variants of gephyrin, a putative glycine receptor-tubulin linker protein","volume":"8","author":"Prior","year":"1992","journal-title":"Neuron"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"22317","DOI":"10.1016\/S0021-9258(18)45707-9","article-title":"Identification and functional expression of a novel ligand binding subunit of the inhibitory glycine receptor","volume":"265","author":"Kuhse","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/0014-5793(91)80557-J","article-title":"Alternative splicing generates two isoforms of the \u03b12 subunit of the inhibitory glycine receptor","volume":"283","author":"Kuhse","year":"1991","journal-title":"FEBS Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1016\/S0021-9258(17)41987-9","article-title":"Structural analysis of mouse glycine receptor alpha subunit genes. Identification and chromosomal localization of a novel variant","volume":"269","author":"Matzenbach","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Leacock, S., Syed, P., James, V.M., Bode, A., Kawakami, K., Keramidas, A., Suster, M., Lynch, J.W., and Harvey, R.J. (2018). Structure\/Function Studies of the \u03b14 Subunit Reveal Evolutionary Loss of a GlyR Subtype Involved in Startle and Escape Responses. Front. Mol. Neurosci., 11.","DOI":"10.3389\/fnmol.2018.00023"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1152\/physrev.00042.2003","article-title":"Molecular structure and function of the glycine receptor chloride channel","volume":"84","author":"Lynch","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.tins.2004.04.002","article-title":"Cys-loop receptors: New twists and turns","volume":"27","author":"Lester","year":"2004","journal-title":"Trends Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4305","DOI":"10.1002\/j.1460-2075.1992.tb05529.x","article-title":"The atypical M2 segment of the beta subunit confers picrotoxinin resistance to inhibitory glycine receptor channels","volume":"11","author":"Pribilla","year":"1992","journal-title":"EMBO J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/s41586-021-04022-z","article-title":"Architecture and assembly mechanism of native glycine receptors","volume":"599","author":"Zhu","year":"2021","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/0896-6273(93)90218-G","article-title":"Assembly of the inhibitory glycine receptor: Identification of amino acid sequence motifs governing subunit stoichiometry","volume":"11","author":"Kuhse","year":"1993","journal-title":"Neuron"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2707","DOI":"10.1016\/j.neuron.2021.08.019","article-title":"Characterization of the subunit composition and structure of adult human glycine receptors","volume":"109","author":"Yu","year":"2021","journal-title":"Neuron"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3729","DOI":"10.1002\/j.1460-2075.1993.tb06050.x","article-title":"Residues within transmembrane segment M2 determine chloride conductance of glycine receptor homo- and hetero-oligomers","volume":"12","author":"Bormann","year":"1993","journal-title":"EMBO J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"19708","DOI":"10.1074\/jbc.273.31.19708","article-title":"The human glycine receptor subunit \u03b13. GLRA3 gene structure, chromosomal localization, and functional characterization of alternative transcripts","volume":"273","author":"Nikolic","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nn1467","article-title":"RNA editing produces glycine receptor \u03b13P185L, resulting in high agonist potency","volume":"8","author":"Meier","year":"2005","journal-title":"Nat. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1016\/S0021-9258(18)52207-9","article-title":"Alternative splicing generates two variants of the alpha 1 subunit of the inhibitory glycine receptor","volume":"266","author":"Malosio","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.bbamcr.2013.11.019","article-title":"Analysis of \u03b13 GlyR single particle tracking in the cell membrane","volume":"1843","author":"Notelaers","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1113\/jphysiol.2003.052142","article-title":"Kinetic properties of the \u03b12 homo-oligomeric glycine receptor impairs a proper synaptic functioning","volume":"553","author":"Mangin","year":"2003","journal-title":"J. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/sj.bjp.0705875","article-title":"Differential agonist sensitivity of glycine receptor \u03b12 subunit splice variants","volume":"143","author":"Miller","year":"2004","journal-title":"Br. J. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0959-4388(03)00062-X","article-title":"Regulation of ion channel\/neurotransmitter receptor function by RNA editing","volume":"13","author":"Seeburg","year":"2003","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Zhu, H. (2022). Structure and Mechanism of Glycine Receptor Elucidated by Cryo-Electron Microscopy. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.925116"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/nature14972","article-title":"Crystal structure of human glycine receptor-\u03b13 bound to antagonist strychnine","volume":"526","author":"Huang","year":"2015","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.str.2017.04.007","article-title":"Crystal Structures of Human GlyR\u03b13 Bound to Ivermectin","volume":"25","author":"Huang","year":"2017","journal-title":"Structure"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/nature14853","article-title":"Glycine receptor mechanism elucidated by electron cryo-microscopy","volume":"526","author":"Du","year":"2015","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1038\/s41467-023-37106-7","article-title":"Conformational transitions and allosteric modulation in a heteromeric glycine receptor","volume":"14","author":"Gibbs","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.cell.2021.01.026","article-title":"Mechanism of gating and partial agonist action in the glycine receptor","volume":"184","author":"Yu","year":"2021","journal-title":"Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1126\/science.8211147","article-title":"Mutation of glycine receptor subunit creates beta-alanine receptor responsive to GABA","volume":"262","author":"Schmieden","year":"1993","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3752","DOI":"10.1038\/s41467-020-17364-5","article-title":"Mechanisms of activation and desensitization of full-length glycine receptor in lipid nanodiscs","volume":"11","author":"Kumar","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Maynard, S.A., and Triller, A. (2019). Inhibitory Receptor Diffusion Dynamics. Front. Mol. Neurosci., 12.","DOI":"10.3389\/fnmol.2019.00313"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1126\/science.1088525","article-title":"Diffusion dynamics of glycine receptors revealed by single-quantum dot tracking","volume":"302","author":"Dahan","year":"2003","journal-title":"Science"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1038\/sj.emboj.7601029","article-title":"Deciphering the structural framework of glycine receptor anchoring by gephyrin","volume":"25","author":"Kim","year":"2006","journal-title":"EMBO J."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Kiss, E., Kirsch, J., Kuhse, J., and Kins, S. (2025). Is the Activation of the Postsynaptic Ligand Gated Glycine- or GABAA Receptors Essential for the Receptor Clustering at Inhibitory Synapses?. Biomedicines, 13.","DOI":"10.3390\/biomedicines13081905"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Dumoulin, A., Triller, A., and Kneussel, M. (2010). Cellular transport and membrane dynamics of the glycine receptor. Front. Mol. Neurosci., 2.","DOI":"10.3389\/neuro.02.028.2009"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"8502","DOI":"10.1523\/JNEUROSCI.1758-06.2006","article-title":"Cytoskeleton regulation of glycine receptor number at synapses and diffusion in the plasma membrane","volume":"26","author":"Charrier","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s00418-021-01973-2","article-title":"Binding of gephyrin to microtubules is regulated by its phosphorylation at Ser270","volume":"156","author":"Zhou","year":"2021","journal-title":"Histochem. Cell Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"30952","DOI":"10.1074\/jbc.M112.349597","article-title":"Phosphorylation of gephyrin in hippocampal neurons by cyclin-dependent kinase CDK5 at Ser-270 is dependent on collybistin","volume":"287","author":"Kuhse","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/nrn3670","article-title":"Gephyrin: A master regulator of neuronal function?","volume":"15","author":"Tyagarajan","year":"2014","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e2500226122","DOI":"10.1073\/pnas.2500226122","article-title":"Competition between glycine and GABAA receptors for gephyrin controls their equilibrium populations at inhibitory synapses","volume":"122","author":"Kostrz","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"16679","DOI":"10.1073\/pnas.1000589107","article-title":"NMDA receptors regulate GABAA receptor lateral mobility and clustering at inhibitory synapses through serine 327 on the \u03b32 subunit","volume":"107","author":"Muir","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3842","DOI":"10.1038\/emboj.2011.276","article-title":"Regulation of glycine receptor diffusion properties and gephyrin interactions by protein kinase C","volume":"30","author":"Specht","year":"2011","journal-title":"EMBO J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/j.1471-4159.2011.07197.x","article-title":"Age-related changes of glycine receptor at the rat hippocampus: From the embryo to the adult","volume":"118","author":"Aroeira","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Kuhse, J., Groeneweg, F., Kins, S., Gorgas, K., Nawrotzki, R., Kirsch, J., and Kiss, E. (2023). Loss of Extrasynaptic Inhibitory Glycine Receptors in the Hippocampus of an AD Mouse Model Is Restored by Treatment with Artesunate. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054623"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1002\/cne.21349","article-title":"Glycine receptors in the striatum, globus pallidus, and substantia nigra of the human brain: An immunohistochemical study","volume":"502","author":"Waldvogel","year":"2007","journal-title":"J. Comp. Neurol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Baer, K., Waldvogel, H.J., Faull, R.L., and Rees, M.I. (2009). Localization of glycine receptors in the human forebrain, brainstem, and cervical spinal cord: An immunohistochemical review. Front. Mol. Neurosci., 2.","DOI":"10.3389\/neuro.02.025.2009"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"102616","DOI":"10.1016\/j.pneurobio.2024.102616","article-title":"Loss of glycine receptors in the nucleus accumbens and ethanol reward in an Alzheimer\u2019s Disease mouse model","volume":"237","author":"Gallegos","year":"2024","journal-title":"Prog. Neurobiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"E7179","DOI":"10.1073\/pnas.1703839114","article-title":"Glycine receptor \u03b13 and \u03b12 subunits mediate tonic and exogenous agonist-induced currents in forebrain","volume":"114","author":"McCracken","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/0896-6273(95)90145-0","article-title":"Identification of a gephyrin binding motif on the glycine receptor beta subunit","volume":"15","author":"Meyer","year":"1995","journal-title":"Neuron"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1523\/JNEUROSCI.4380-03.2004","article-title":"Intracellular association of glycine receptor with gephyrin increases its plasma membrane accumulation rate","volume":"24","author":"Hanus","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1523\/JNEUROSCI.1661-03.2004","article-title":"Gephyrin is critical for glycine receptor clustering but not for the formation of functional GABAergic synapses in hippocampal neurons","volume":"24","author":"Logan","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1007\/s00429-018-1607-3","article-title":"Extrasynaptic homomeric glycine receptors in neurons of the rat trigeminal mesencephalic nucleus","volume":"223","author":"Bae","year":"2018","journal-title":"Brain Struct. Funct."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1021\/cb500303a","article-title":"Modulation of gephyrin-glycine receptor affinity by multivalency","volume":"9","author":"Maric","year":"2014","journal-title":"ACS Chem. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2400","DOI":"10.1152\/jn.1997.77.5.2400","article-title":"Pharmacological evidence for two types of postsynaptic glycinergic receptors on the Mauthner cell of 52-h-old zebrafish larvae","volume":"77","author":"Legendre","year":"1997","journal-title":"J. Neurophysiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"RP109447","DOI":"10.7554\/eLife.109447","article-title":"Single molecule counting detects low-copy glycine receptors in hippocampal and striatal synapses","volume":"14","author":"Camuso","year":"2026","journal-title":"eLife"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"16016","DOI":"10.1074\/jbc.M701502200","article-title":"Mechanisms for picrotoxinin and picrotin blocks of \u03b12 homomeric glycine receptors","volume":"282","author":"Wang","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1111\/j.1471-4159.2007.04850.x","article-title":"A proposed structural basis for picrotoxinin and picrotin binding in the glycine receptor pore","volume":"103","author":"Yang","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1016\/S0026-895X(25)09863-3","article-title":"Biphasic modulation of the strychnine-sensitive glycine receptor by Zn2+","volume":"46","author":"Bloomenthal","year":"1994","journal-title":"Mol. Pharmacol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1152\/jn.00714.2013","article-title":"Strychnine-sensitive glycine receptors on pyramidal neurons in layers II\/III of the mouse prefrontal cortex are tonically activated","volume":"112","author":"Salling","year":"2014","journal-title":"J. Neurophysiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.brainres.2012.01.050","article-title":"Changes in glycine receptor subunit expression in forebrain regions of the Wistar rat over development","volume":"1446","author":"Jonsson","year":"2012","journal-title":"Brain Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1172\/JCI71472","article-title":"Changes in neural network homeostasis trigger neuropsychiatric symptoms","volume":"124","author":"Winkelmann","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1093\/cercor\/bhw001","article-title":"Identification of Parvalbumin Interneurons as Cellular Substrate of Fear Memory Persistence","volume":"26","author":"Semtner","year":"2016","journal-title":"Cereb. Cortex"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Molchanova, S.M., Comhair, J., Karadurmus, D., Piccart, E., Harvey, R.J., Rigo, J.M., Schiffmann, S.N., Br\u00f4ne, B., and Gall, D. (2018). Tonically Active \u03b12 Subunit-Containing Glycine Receptors Regulate the Excitability of Striatal Medium Spiny Neurons. Front. Mol. Neurosci., 10.","DOI":"10.3389\/fnmol.2017.00442"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3622","DOI":"10.1111\/j.1742-4658.2010.07754.x","article-title":"Calcium-dependent mitochondrial function and dysfunction in neurons","volume":"277","author":"Pivovarova","year":"2010","journal-title":"FEBS J."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1007\/s12035-025-05465-5","article-title":"Role of Mitochondrial Calcium Dysregulation in Alzheimer\u2019s Disease Pathogenesis","volume":"63","author":"Ebrahimi","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/sj.npp.1301449","article-title":"Glycine uptake regulates hippocampal network activity via glycine receptor-mediated tonic inhibition","volume":"33","author":"Zhang","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"5749","DOI":"10.1113\/jphysiol.2012.241299","article-title":"Glycine receptors support excitatory neurotransmitter release in developing mouse visual cortex","volume":"590","author":"Kunz","year":"2012","journal-title":"J. Physiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"107400","DOI":"10.1016\/j.isci.2023.107400","article-title":"Dopamine-mediated striatal activity and function is enhanced in GlyR\u03b12 knockout animals","volume":"26","author":"Devoght","year":"2023","journal-title":"iScience"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Yi, G.S., Wang, J., Li, H.Y., Wei, X.L., and Deng, B. (2016). Metabolic Energy of Action Potentials Modulated by Spike Frequency Adaptation. Front. Neurosci., 10.","DOI":"10.3389\/fnins.2016.00534"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1002\/bies.201500004","article-title":"Neuronal hyperactivity\u2014A key defect in Alzheimer\u2019s disease?","volume":"37","author":"Busche","year":"2015","journal-title":"Bioessays"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"19606","DOI":"10.1038\/s41598-020-76456-w","article-title":"Changes in neuronal excitability and synaptic transmission in nucleus accumbens in a transgenic Alzheimer\u2019s disease mouse model","volume":"10","author":"Gallegos","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.cell.2012.06.029","article-title":"Synaptic and extrasynaptic NMDA receptors are gated by different endogenous coagonists","volume":"150","author":"Papouin","year":"2012","journal-title":"Cell"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/307462a0","article-title":"Magnesium gates glutamate-activated channels in mouse central neurones","volume":"307","author":"Nowak","year":"1984","journal-title":"Nature"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1007\/s11064-010-0174-7","article-title":"Presynaptic glycine receptors influence plasma membrane potential and glutamate release","volume":"35","author":"Waseem","year":"2010","journal-title":"Neurochem. Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"102856","DOI":"10.1016\/j.pneurobio.2025.102856","article-title":"Glycine and glycine transport control dendritic excitability and spiking","volume":"256","author":"Bohmbach","year":"2026","journal-title":"Prog. Neurobiol."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Raiteri, L., Cerminara, M., Puliti, A., and Pittaluga, A. (2025). Glycine Release Is Upregulated by Metabotropic Glutamate Receptor 1 in Mouse Hippocampus. Biomedicines, 13.","DOI":"10.3390\/biomedicines13123106"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1038\/npp.2011.86","article-title":"Role of glycine receptors in glycine-induced LTD in hippocampal CA1 pyramidal neurons","volume":"36","author":"Chen","year":"2011","journal-title":"Neuropsychopharmacology"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.tins.2023.05.002","article-title":"Excitatory GluN1\/GluN3A glycine receptors (eGlyRs) in brain signaling","volume":"46","author":"Bossi","year":"2023","journal-title":"Trends Neurosci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e2501118122","DOI":"10.1073\/pnas.2501118122","article-title":"Excitatory glycine receptors control ventral hippocampus synaptic plasticity and anxiety-related behaviors","volume":"122","author":"Pizzamiglio","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Zhang, W., Zhao, M., Dai, J., Zhuo, L., Ye, H., Wang, J., and Wang, W. (2024). Non-classical NMDA receptor subunit GluN3A in a specialized hippocampal region regulates stress-coping strategies in mice. bioRxiv.","DOI":"10.1101\/2024.04.24.590964"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Consens, M.E., Chen, Y., Menon, V., Wang, Y., Schneider, J.A., De Jager, P.L., Bennett, D.A., Tripathy, S.J., and Felsky, D. (2022). Bulk and Single-Nucleus Transcriptomics Highlight Intra-Telencephalic and Somatostatin Neurons in Alzheimer\u2019s Disease. Front. Mol. Neurosci., 15.","DOI":"10.3389\/fnmol.2022.903175"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1002\/alz.12398","article-title":"Pathogenesis of sporadic Alzheimer\u2019s disease by deficiency of NMDA receptor subunit GluN3A","volume":"18","author":"Zhong","year":"2022","journal-title":"Alzheimers Dement."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1016\/j.neuron.2022.05.016","article-title":"GluN3A excitatory glycine receptors control adult cortical and amygdalar circuits","volume":"110","author":"Bossi","year":"2022","journal-title":"Neuron"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1126\/science.aax1522","article-title":"Control of aversion by glycine-gated GluN1\/GluN3A NMDA receptors in the adult medial habenula","volume":"366","author":"Otsu","year":"2019","journal-title":"Science"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1016\/j.neuron.2016.02.030","article-title":"Chloride Regulation: A Dynamic Equilibrium Crucial for Synaptic Inhibition","volume":"89","author":"Doyon","year":"2016","journal-title":"Neuron"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Ji, J., Choi, C., Bope, C.E., Dengler, J.S., Moss, S.J., and Smalley, J.L. (2025). KCC2 inhibition and neuronal hyperexcitability promote extrinsic apoptosis dependent upon C1q. Front. Mol. Neurosci., 18.","DOI":"10.3389\/fnmol.2025.1645428"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"147071","DOI":"10.1016\/j.brainres.2020.147071","article-title":"Cross-talk pattern between GABAA- and glycine-receptors in CNS neurons is shaped by their relative expression levels","volume":"1748","author":"Tang","year":"2020","journal-title":"Brain Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.neuroscience.2019.07.036","article-title":"Tuning GABAergic Inhibition: Gephyrin Molecular Organization and Functions","volume":"439","author":"Pizzarelli","year":"2020","journal-title":"Neuroscience"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Kasaragod, V.B., and Schindelin, H. (2018). Structure-Function Relationships of Glycine and GABAA Receptors and Their Interplay With the Scaffolding Protein Gephyrin. Front. Mol. Neurosci., 11.","DOI":"10.3389\/fnmol.2018.00317"},{"key":"ref_115","unstructured":"World Health Organization (2023). Dementia, World Health Organization. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/dementia."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"20150429","DOI":"10.1098\/rstb.2015.0429","article-title":"Impairments of neural circuit function in Alzheimer\u2019s disease","volume":"371","author":"Busche","year":"2016","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Burns, A.P., Duran, M.I., Fortel, I., Lazarov, O., Zhan, L., Bendlin, B., and Leow, A. (2026). Excitation-inhibition homeostasis in Alzheimer\u2019s disease: A selective multiscale review of mechanisms, sex differences, and therapeutic opportunities. Neuropsychopharmacology.","DOI":"10.1038\/s41386-026-02334-0"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S1474-4422(17)30044-3","article-title":"Epileptic activity in Alzheimer\u2019s disease: Causes and clinical relevance","volume":"16","author":"Vossel","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.ibneur.2025.05.005","article-title":"Effect of neuroinflammation on the progression of Alzheimer\u2019s disease and its significant ramifications for novel anti-inflammatory treatments","volume":"18","author":"Kamila","year":"2025","journal-title":"IBRO Neurosci. Rep."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.neulet.2013.12.037","article-title":"Glycine receptor in hippocampal neurons as a target for action of extracellular cyclic nucleotides","volume":"561","author":"Bukanova","year":"2014","journal-title":"Neurosci. Lett."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.brainres.2016.09.016","article-title":"Functional modulation of strychnine-sensitive glycine receptors in rat hippocampal pyramidal neurons by amyloid-\u03b2 protein (1\u201342)","volume":"1651","author":"Bukanova","year":"2016","journal-title":"Brain Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1038\/s41380-024-02789-x","article-title":"Cannabidiol ameliorates cognitive decline in 5\u00d7FAD mouse model of Alzheimer\u2019s disease through potentiating the function of extrasynaptic glycine receptors","volume":"30","author":"Jin","year":"2025","journal-title":"Mol. Psychiatry"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1111\/nan.12674","article-title":"Identification of intraneuronal amyloid beta oligomers in locus coeruleus neurons of Alzheimer\u2019s patients and their potential impact on inhibitory neurotransmitter receptors and neuronal excitability","volume":"47","author":"Kelly","year":"2021","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Hansen, N., Bartels, C., St\u00f6cker, W., Wiltfang, J., and Fitzner, D. (2022). Impaired Verbal Memory Recall in Patients With Axonal Degeneration and Serum Glycine-Receptor Autoantibodies-Case Series. Front. Psychiatry, 12.","DOI":"10.3389\/fpsyt.2021.778684"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Hu, J., Sha, W., Yuan, S., Wu, J., and Huang, Y. (2023). Aggregation, Transmission, and Toxicity of the Microtubule-Associated Protein Tau: A Complex Comprehension. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241915023"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.neuron.2017.05.026","article-title":"Physico-Pathologic Mechanisms Involved in Neurodegeneration: Misfolded Protein-Plasma Membrane Interactions","volume":"95","author":"Shrivastava","year":"2017","journal-title":"Neuron"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Jia, S., Li, Q., Rui, X., Qin, W., Zhang, W., Dou, J., and Zhang, X. (2025). The ubiquitin-proteasome system in Alzheimer\u2019s disease: Mechanism of action and current status of treatment. Front. Aging Neurosci., 17.","DOI":"10.3389\/fnagi.2025.1730206"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1038\/s42255-025-01365-z","article-title":"The Neurolipid Atlas: A lipidomics resource for neurodegenerative diseases","volume":"7","author":"Feringa","year":"2025","journal-title":"Nat. Metab."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"e77850","DOI":"10.7554\/eLife.77850","article-title":"Altered excitatory and inhibitory neuronal subpopulation parameters are distinctly associated with tau and amyloid in Alzheimer\u2019s disease","volume":"11","author":"Ranasinghe","year":"2022","journal-title":"eLife"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1002\/glia.23098","article-title":"Glutamate transporter-associated anion channels adjust intracellular chloride concentrations during glial maturation","volume":"65","author":"Untiet","year":"2017","journal-title":"Glia"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Van den Eynden, J., Ali, S.S., Horwood, N., Carmans, S., Br\u00f4ne, B., Hellings, N., Steels, P., Harvey, R.J., and Rigo, J.M. (2009). Glycine and glycine receptor signalling in non-neuronal cells. Front. Mol. Neurosci., 2.","DOI":"10.3389\/neuro.02.009.2009"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Morais, T.P., Coelho, D., Vaz, S.H., Sebasti\u00e3o, A.M., and Valente, C.A. (2018). Glycine Receptor Activation Impairs ATP-Induced Calcium Transients in Cultured Cortical Astrocytes. Front. Mol. Neurosci., 10.","DOI":"10.3389\/fnmol.2017.00444"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.brainresbull.2012.12.002","article-title":"Mechanisms of glycine release, which build up synaptic and extrasynaptic glycine levels: The role of synaptic and non-synaptic glycine transporters","volume":"93","author":"Harsing","year":"2013","journal-title":"Brain Res. Bull."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"e00540","DOI":"10.1016\/j.neurot.2025.e00540","article-title":"Astrocyte and oligodendrocyte pathology in Alzheimer\u2019s disease","volume":"22","author":"Ziar","year":"2025","journal-title":"Neurotherapeutics"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1177\/13872877251411561","article-title":"The role of astrocytes in Alzheimer\u2019s disease: Pathophysiology, biomarkers, and therapeutic potential","volume":"110","author":"Abedin","year":"2026","journal-title":"J. Alzheimers Dis."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Hossain, M.K., and Kim, H.R. (2026). Taurine as an Early-Phase Disease-Modifying Candidate for Alzheimer\u2019s Disease. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27041871"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Gautam, D., Naik, U.P., Naik, M.U., Yadav, S.K., Chaurasia, R.N., and Dash, D. (2023). Glutamate Receptor Dysregulation and Platelet Glutamate Dynamics in Alzheimer\u2019s and Parkinson\u2019s Diseases: Insights into Current Medications. Biomolecules, 13.","DOI":"10.3390\/biom13111609"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"5422","DOI":"10.1038\/ncomms6422","article-title":"Metabotropic P2Y1 receptor signalling mediates astrocytic hyperactivity in vivo in an Alzheimer\u2019s disease mouse model","volume":"5","author":"Delekate","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1523\/JNEUROSCI.19-02-00562.1999","article-title":"Synthesis of the antioxidant glutathione in neurons: Supply by astrocytes of CysGly as precursor for neuronal glutathione","volume":"19","author":"Dringen","year":"1999","journal-title":"J. Neurosci."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.4049\/jimmunol.1801166","article-title":"Glycine Exhibits Neuroprotective Effects in Ischemic Stroke in Rats through the Inhibition of M1 Microglial Polarization via the NF-\u03baB p65\/Hif-1\u03b1 Signaling Pathway","volume":"202","author":"Liu","year":"2019","journal-title":"J. Immunol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1186\/s12974-020-01941-y","article-title":"Blocking glycine receptors reduces neuroinflammation and restores neurotransmission in cerebellum through ADAM17-TNFR1-NF-\u03ba\u03b2 pathway","volume":"17","author":"Arenas","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Egger, F., Jakab, M., Fuchs, J., Oberascher, K., Brachtl, G., Ritter, M., Kerschbaum, H.H., and Gaisberger, M. (2020). Effect of Glycine on BV-2 Microglial Cells Treated with Interferon-\u03b3 and Lipopolysaccharide. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030804"},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Thakur, V., Chokpapone, Y.M., Mishra, R., Evbuomwan, O., Lopez, L., Guerrero, C., Chavez, A., Carrizales, I., Rodriguez, B.J., and Lavezo, J. (2026). Glycine receptors in circulating white blood cells regulated by neuroinflammation. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1749275"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/ni.1636","article-title":"The NALP3 inflammasome is involved in the innate immune response to amyloid-beta","volume":"9","author":"Halle","year":"2008","journal-title":"Nat. Immunol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s40478-019-0754-y","article-title":"Intersection of pathological tau and microglia at the synapse","volume":"7","author":"Vogels","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"10180","DOI":"10.1523\/JNEUROSCI.3591-05.2005","article-title":"Deletion of the prostaglandin E2 EP2 receptor reduces oxidative damage and amyloid burden in a model of Alzheimer\u2019s disease","volume":"25","author":"Liang","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1002\/syn.20963","article-title":"Glycine receptor internalization by protein kinases activation","volume":"65","author":"Salceda","year":"2011","journal-title":"Synapse"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"e70180","DOI":"10.1111\/ejn.70180","article-title":"Amyloid-Beta Pathology Increases Synaptic Engulfment by Glia in Feline Cognitive Dysfunction Syndrome: A Naturally Occurring Model of Alzheimer\u2019s Disease","volume":"62","author":"McGeachan","year":"2025","journal-title":"Eur. J. Neurosci."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1007\/s00726-014-1745-8","article-title":"Glycine modulates membrane potential, cell volume, and phagocytosis in murine microglia","volume":"46","author":"Komm","year":"2014","journal-title":"Amino Acids"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1159\/000494646","article-title":"Glycine Induces Migration of Microglial BV-2 Cells via SNAT-Mediated Cell Swelling","volume":"50","author":"Kittl","year":"2018","journal-title":"Cell Physiol. Biochem."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1111\/j.1532-5415.1992.tb02019.x","article-title":"Milacemide: A placebo-controlled study in senile dementia of the Alzheimer type","volume":"40","author":"Dysken","year":"1992","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.cell.2016.11.010","article-title":"Artemisinins Target GABAA Receptor Signaling and Impair \u03b1 Cell Identity","volume":"168","author":"Li","year":"2017","journal-title":"Cell"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"103624","DOI":"10.1016\/j.mcn.2021.103624","article-title":"Artesunate restores the levels of inhibitory synapse proteins and reduces amyloid-\u03b2 and C-terminal fragments (CTFs) of the amyloid precursor protein in an AD-mouse model","volume":"113","author":"Kiss","year":"2021","journal-title":"Mol. Cell Neurosci."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Kiss, E., Kins, S., Gorgas, K., Venczel Szak\u00e1cs, K.H., Kirsch, J., and Kuhse, J. (2024). Another Use for a Proven Drug: Experimental Evidence for the Potential of Artemisinin and Its Derivatives to Treat Alzheimer\u2019s Disease. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25084165"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"12556","DOI":"10.1074\/jbc.M011264200","article-title":"Ivermectin, an unconventional agonist of the glycine receptor chloride channel","volume":"276","author":"Shan","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1080\/17582024.2025.2554374","article-title":"Neuroprotective effects of ivermectin on Alzheimer\u2019s model induced by streptozotocin in rats","volume":"16","author":"Farajpour","year":"2026","journal-title":"Neurodegener. Dis. Manag."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"eaeb2036","DOI":"10.1126\/sciadv.aeb2036","article-title":"Structural basis for domain coupling in heteromeric glycine receptors revealed by an atypical allosteric agonist","volume":"12","author":"Gibbs","year":"2026","journal-title":"Sci. Adv."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1113\/JP275236","article-title":"Ivermectin and its target molecules: Shared and unique modulation mechanisms of ion channels and receptors by ivermectin","volume":"596","author":"Chen","year":"2018","journal-title":"J. Physiol."},{"key":"ref_160","unstructured":"World Health Organization (2023). WHO Guidelines for Malaria, 14 March 2023 (WHO\/UCN\/GMP\/2023.01), WHO."},{"key":"ref_161","unstructured":"Food and Drug Administration (2026, May 10). FDA Approves First Drug Comprised of an Active Ingredient Derived from Marijuana to Treat Rare, Severe Forms of Epilepsy. Available online: https:\/\/www.prnewswire.com\/news-releases\/fda-approves-first-drug-comprised-of-an-active-ingredient-derived-from-marijuana-to-treat-rare-severe-forms-of-epilepsy-300671667.html."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1146\/annurev.mi.45.100191.002305","article-title":"Ivermectin as an antiparasitic agent for use in humans","volume":"45","author":"Campbell","year":"1991","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"382","DOI":"10.4269\/ajtmh.17-0042","article-title":"Serious Neurological Adverse Events after Ivermectin-Do They Occur beyond the Indication of Onchocerciasis?","volume":"98","author":"Chandler","year":"2018","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"e70061","DOI":"10.1111\/jnc.70061","article-title":"Milestone Review: Unlocking the Proteomics of Glycine Receptor Complexes","volume":"169","author":"Fraser","year":"2025","journal-title":"J. Neurochem."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"5515","DOI":"10.1038\/s41598-025-90209-7","article-title":"Allosteric modulation and direct activation of glycine receptors by a tricyclic sulfonamide","volume":"15","author":"Lara","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1177\/1087057115590575","article-title":"Positive Modulation of the Glycine Receptor by Means of Glycine Receptor-Binding Aptamers","volume":"20","author":"Shalaly","year":"2015","journal-title":"J. Biomol. Screen."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"118527","DOI":"10.1016\/j.biopha.2025.118527","article-title":"Taurine suppresses A\u03b2 aggregation and attenuates Alzheimer\u2019s disease pathologies in 5XFAD mice and patient-derived cerebral organoids","volume":"191","author":"Lee","year":"2025","journal-title":"BioMed. Pharmacother."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1113\/jphysiol.2001.013147","article-title":"Beta-alanine and taurine as endogenous agonists at glycine receptors in rat hippocampus in vitro","volume":"539","author":"Mori","year":"2002","journal-title":"J. Physiol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.1007\/s11064-024-04190-0","article-title":"GlyT1 Inhibition by NFPS Promotes Neuroprotection in Amyloid-\u03b2-Induced Alzheimer\u2019s Disease Animal Model","volume":"49","author":"Ulrich","year":"2024","journal-title":"Neurochem. Res."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13195-023-01163-3","article-title":"Efficacy and safety of the novel GlyT1 inhibitor BI 425809 in Alzheimer\u2019s dementia: A randomized controlled trial","volume":"15","author":"Wunderlich","year":"2023","journal-title":"Alzheimers Res. Ther."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jagp.2025.10.011","article-title":"A Randomized Controlled Trial of the Safety and Efficacy of Dronabinol for Agitation in Alzheimer\u2019s Disease","volume":"34","author":"Rosenberg","year":"2026","journal-title":"Am. J. Geriatr. Psychiatry"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1212\/WNL.0000000000001675","article-title":"Tetrahydrocannabinol for neuropsychiatric symptoms in dementia: A randomized controlled trial","volume":"84","author":"Ahmed","year":"2015","journal-title":"Neurology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6306\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T06:59:50Z","timestamp":1784185190000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6306"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,15]]},"references-count":172,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27146306"],"URL":"https:\/\/doi.org\/10.3390\/ijms27146306","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,15]]}}}