{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:16:03Z","timestamp":1785406563000,"version":"3.56.0"},"reference-count":52,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000964","name":"the Science and Engineering Research Board, Department of Science and Technology","doi-asserted-by":"publisher","award":["SERB-DST CRG\/2018\/004089"],"award-info":[{"award-number":["SERB-DST CRG\/2018\/004089"]}],"id":[{"id":"10.13039\/100000964","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Department of Biotechnology","award":["BT\/PR20904\/MED\/122\/58\/2016"],"award-info":[{"award-number":["BT\/PR20904\/MED\/122\/58\/2016"]}]},{"award":["BT\/PR20904\/MED\/122\/58\/2016"],"award-info":[{"award-number":["BT\/PR20904\/MED\/122\/58\/2016"]}],"id":[{"id":"https:\/\/ror.org\/03tjsyq23","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the University Grants Commission","award":["19\/06\/2016(i)EU-V"],"award-info":[{"award-number":["19\/06\/2016(i)EU-V"]}]},{"award":["19\/06\/2016(i)EU-V"],"award-info":[{"award-number":["19\/06\/2016(i)EU-V"]}],"id":[{"id":"https:\/\/ror.org\/04p800546","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glutamate excitotoxicity is a critical pathological mechanism underlying neuronal death in ischemic stroke, epilepsy, and neurodegenerative diseases. Caveolin-1 (Cav-1), a structural protein of caveolae membrane microdomains, has emerged as a potential modulator of neuronal survival, yet its precise mechanisms in excitotoxicity remain incompletely understood. In this study, we investigated the role of Cav-1 in regulating glutamate-induced calcium dysregulation, reactive oxygen species (ROS) generation, and mitochondrial dysfunction in primary hippocampal neurons. Using Cav-1 overexpression (Cav-1OE) and Cav-1 knockdown (Cav-1KD) approaches, we demonstrate that Cav-1OE significantly attenuates glutamate-stimulated intracellular Ca2+ elevation, reduces ROS generation, and prevents mitochondrial membrane potential (\u03a8m) depolarization. Further investigation revealed that Cav-1OE reduces, while Cav-1KD enhances, calcium responses mediated by NMDA, AMPA, and KA receptors. These findings establish that Cav-1 functionally attenuates excitotoxic signaling by negatively regulating ionotropic glutamate receptor-mediated Ca2+ influx.<\/jats:p>","DOI":"10.3390\/ijms27125637","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:09:17Z","timestamp":1782270557000},"page":"5637","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Caveolin-1 Attenuates Excitotoxic Signaling by Regulating NMDA, AMPA, and Kainate Receptor-Mediated Calcium Influx in Hippocampal Neuronal Cultures"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8339-7282","authenticated-orcid":false,"given":"Swapna Kannothum","family":"Kandy","sequence":"first","affiliation":[{"name":"Department of Biophysics, National Institute of Mental Health and Neuroscience (NIMHANS), Bengaluru 560029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7820-1513","authenticated-orcid":false,"given":"Madhura Milind","family":"Nimonkar","sequence":"additional","affiliation":[{"name":"Department of Biophysics, National Institute of Mental Health and Neuroscience (NIMHANS), Bengaluru 560029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0289-7339","authenticated-orcid":false,"given":"Suravi Sasmita","family":"Dash","sequence":"additional","affiliation":[{"name":"Department of Biophysics, National Institute of Mental Health and Neuroscience (NIMHANS), Bengaluru 560029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashanth N.","family":"Vashista","sequence":"additional","affiliation":[{"name":"Department of Biophysics, National Institute of Mental Health and Neuroscience (NIMHANS), Bengaluru 560029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5196-6436","authenticated-orcid":false,"given":"Bhupesh","family":"Mehta","sequence":"additional","affiliation":[{"name":"Department of Biophysics, National Institute of Mental Health and Neuroscience (NIMHANS), Bengaluru 560029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9783-2046","authenticated-orcid":false,"given":"Yogananda S.","family":"Markandeya","sequence":"additional","affiliation":[{"name":"Department of Biophysics, National Institute of Mental Health and Neuroscience (NIMHANS), Bengaluru 560029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"160","DOI":"10.33545\/26174693.2025.v9.i3b.7522","article-title":"Glutamate excitotoxicity, NMDA receptor overactivation, and calcium-mediated neuronal death mechanisms in ischemic stroke","volume":"9","author":"Adeyemi","year":"2025","journal-title":"Int. J. Adv. Biochem. Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Arnold, F.J., Putka, A.F., Raychaudhuri, U., Hsu, S., Bedlack, R.S., Bennett, C.L., and La Spada, A.R. (2024). Revisiting Glutamate Excitotoxicity in Amyotrophic Lateral Sclerosis and Age-Related Neurodegeneration. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25115587"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Hou, J., Klippel, K., and Bose, P. (2025). Glutamate Excitotoxicity: A Key Secondary Injury Mechanism of Traumatic Brain Injury and Spinal Cord Injury. Front. Biosci., 30.","DOI":"10.31083\/FBL38904"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.jvir.2017.11.026","article-title":"Multisociety Consensus Quality Improvement Revised Consensus Statement for Endovascular Therapy of Acute Ischemic Stroke: From the American Association of Neurological Surgeons (AANS), American Society of Neuroradiology (ASNR), Cardiovascular and Interventional Radiology Society of Europe (CIRSE), Canadian Interventional Radiology Association (CIRA), Congress of Neurological Surgeons (CNS), European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (ESNR), European Stroke Organization (ESO), Society for Cardiovascular Angiography and Interventions (SCAI), Society of Interventional Radiology (SIR), Society of NeuroInterventional Surgery (SNIS), and World Stroke Organization (WSO)","volume":"29","author":"Sacks","year":"2018","journal-title":"J. Vasc. Interv. Radiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s13041-021-00764-z","article-title":"Caveolin-1 deficiency impairs synaptic transmission in hippocampal neurons","volume":"14","author":"Koh","year":"2021","journal-title":"Mol. Brain"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5177","DOI":"10.1021\/acs.jpcb.0c02962","article-title":"Sphingomyelin Effects in Caveolin-1 Mediated Membrane Curvature","volume":"124","author":"Krishna","year":"2020","journal-title":"J. Phys. Chem. B"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1186\/s12964-024-01876-4","article-title":"Lipid rafts, caveolae, and epidermal growth factor receptor family: Friends or foes?","volume":"22","author":"Ruzzi","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Choi, D.W. (2020). Excitotoxicity: Still Hammering the Ischemic Brain in 2020. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.579953"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.tins.2021.01.001","article-title":"Excitotoxicity Revisited: Mitochondria on the Verge of a Nervous Breakdown","volume":"44","author":"Plotegher","year":"2021","journal-title":"Trends Neurosci."},{"key":"ref_10","first-page":"2504","article-title":"Excitotoxicity, Oxytosis\/Ferroptosis, and Neurodegeneration: Emerging Insights into Mitochondrial Mechanisms","volume":"16","author":"Khan","year":"2024","journal-title":"Aging Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.tins.2024.06.003","article-title":"Physiological and pathological roles of caveolins in the central nervous system","volume":"47","author":"Badaut","year":"2024","journal-title":"Trends Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s10753-019-01154-3","article-title":"Nateglinide Exerts Neuroprotective Effects via Downregulation of HIF-1\u03b1\/TIM-3 Inflammatory Pathway and Promotion of Caveolin-1 Expression in the Rat\u2019s Hippocampus Subjected to Focal Cerebral Ischemia\/Reperfusion Injury","volume":"43","author":"Saad","year":"2020","journal-title":"Inflammation"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1089\/thy.2020.0238","article-title":"Downregulation of Caveolin-1 and Upregulation of Deiodinase 3, Associated with Hypoxia-Inducible Factor-1alpha Increase, Are Involved in the Oxidative Stress of Graves\u2019 Orbital Adipocytes","volume":"31","author":"Joris","year":"2021","journal-title":"Thyroid"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.neubiorev.2021.06.044","article-title":"Caveolin-1, a novel player in cognitive decline","volume":"129","author":"Tang","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Armada-Moreira, A., Gomes, J.I., Pina, C.C., Savchak, O.K., Goncalves-Ribeiro, J., Rei, N., Pinto, S., Morais, T.P., Martins, R.S., and Ribeiro, F.F. (2020). Going the Extra (Synaptic) Mile: Excitotoxicity as the Road Toward Neurodegenerative Diseases. Front. Cell. Neurosci., 14.","DOI":"10.3389\/fncel.2020.00090"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"12973","DOI":"10.1523\/JNEUROSCI.1597-12.2012","article-title":"Activation of neuronal NMDA receptors induces superoxide-mediated oxidative stress in neighboring neurons and astrocytes","volume":"32","author":"Reyes","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40035-021-00278-7","article-title":"Excitotoxicity, calcium and mitochondria: A triad in synaptic neurodegeneration","volume":"11","author":"Verma","year":"2022","journal-title":"Transl. Neurodegener."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"17045","DOI":"10.1038\/cddiscovery.2017.45","article-title":"DS16570511 is a small-molecule inhibitor of the mitochondrial calcium uniporter","volume":"3","author":"Kon","year":"2017","journal-title":"Cell Death Discov."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1007\/s12035-018-1204-8","article-title":"Pharmacological Sequestration of Mitochondrial Calcium Uptake Protects Neurons Against Glutamate Excitotoxicity","volume":"56","author":"Angelova","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/nep3.46","article-title":"Glutamate and excitotoxicity in central nervous system disorders: Ionotropic glutamate receptors as a target for neuroprotection","volume":"2","year":"2024","journal-title":"Neuroprotection"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100543","DOI":"10.1016\/j.mcpro.2023.100543","article-title":"N-Terminomic Changes in Neurons During Excitotoxicity Reveal Proteolytic Events Associated With Synaptic Dysfunctions and Potential Targets for Neuroprotection","volume":"22","author":"Ameen","year":"2023","journal-title":"Mol. Cell. Proteom."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kandy, S.K., Nimonkar, M.M., Dash, S.S., Mehta, B., and Markandeya, Y.S. (2022). Astaxanthin Protection against Neuronal Excitotoxicity via Glutamate Receptor Inhibition and Improvement of Mitochondrial Function. Mar. Drugs, 20.","DOI":"10.3390\/md20100645"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Byrne, D.P., Dart, C., and Rigden, D.J. (2012). Evaluating caveolin interactions: Do proteins interact with the caveolin scaffolding domain through a widespread aromatic residue-rich motif?. PLoS ONE, 7, Correction in PLoS ONE\u00a02013, 8, 2.","DOI":"10.1371\/annotation\/2c275a1b-2d36-4492-b36a-192bddf14f78"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1523\/JNEUROSCI.1161-14.2015","article-title":"Caveolin-1 in the anterior cingulate cortex modulates chronic neuropathic pain via regulation of NMDA receptor 2B subunit","volume":"35","author":"Yang","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1007\/s00213-020-05564-2","article-title":"Caveolin-1 regulates medium spiny neuron structural and functional plasticity","volume":"237","author":"Eisinger","year":"2020","journal-title":"Psychopharmacology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/nrn2059","article-title":"Lipid raft microdomains and neurotransmitter signalling","volume":"8","author":"Allen","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/jnr.10556","article-title":"Glutamate regulates caveolin expression in rat hippocampal neurons","volume":"72","author":"Bu","year":"2003","journal-title":"J. Neurosci. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3823","DOI":"10.1096\/fj.14-252320","article-title":"Regulation of intracellular signaling and function by caveolin","volume":"28","author":"Fridolfsson","year":"2014","journal-title":"FASEB J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.cub.2011.03.030","article-title":"Caveolin-1 deficiency causes cholesterol-dependent mitochondrial dysfunction and apoptotic susceptibility","volume":"21","author":"Bosch","year":"2011","journal-title":"Curr. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.ceca.2011.04.007","article-title":"Mitochondrial permeability transition in Ca(2+)-dependent apoptosis and necrosis","volume":"50","author":"Rasola","year":"2011","journal-title":"Cell Calcium"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1111\/epi.14190","article-title":"Lamotrigine-resistant corneal-kindled mice: A model of pharmacoresistant partial epilepsy for moderate-throughput drug discovery","volume":"59","author":"Koneval","year":"2018","journal-title":"Epilepsia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"36","DOI":"10.37349\/ent.2022.00017","article-title":"Various facets of excitotoxicity","volume":"2","author":"Glaser","year":"2022","journal-title":"Explor. Neuroprotective Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1021\/acsomega.5c05841","article-title":"Glutamate Receptor Agonists as Triggers of Neurotoxicity: Decoding Pathways of Five Neurotoxins and Potential Therapeutic Targets","volume":"11","author":"Turcatel","year":"2026","journal-title":"ACS Omega"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Nicosia, N., Giovenzana, M., Misztak, P., Mingardi, J., and Musazzi, L. (2024). Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25126521"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3403","DOI":"10.1096\/fj.201601288RRR","article-title":"Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma","volume":"31","author":"Egawa","year":"2017","journal-title":"FASEB J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1159\/000445637","article-title":"Alterations in Caveolin-1 Expression and Receptor-Operated Ca2+ Entry in the Aortas of Rats with Pulmonary Hypertension","volume":"39","author":"Mu","year":"2016","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1161\/01.RES.0000260180.42709.29","article-title":"Caveolin-1 deficiency increases cerebral ischemic injury","volume":"100","author":"Jasmin","year":"2007","journal-title":"Circ. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1016\/j.ajpath.2010.12.023","article-title":"Caveolin-1 deletion reduces early brain injury after experimental intracerebral hemorrhage","volume":"178","author":"Chang","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.neuron.2018.10.018","article-title":"The AMPA Receptor Code of Synaptic Plasticity","volume":"100","author":"Diering","year":"2018","journal-title":"Neuron"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.neuron.2004.09.012","article-title":"LTP and LTD: An embarrassment of riches","volume":"44","author":"Malenka","year":"2004","journal-title":"Neuron"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/nrn2867","article-title":"Long-term depression in the CNS","volume":"11","author":"Collingridge","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Stephen, T.K.L., Cofresi, L.A., Quiroz, E., Owusu-Ansah, K., Ibrahim, Y., Qualls, E., Marshall, J., Li, W., Shetti, A., and Bonds, J.A. (2023). Caveolin-1 Autonomously Regulates Hippocampal Neurogenesis Via Mitochondrial Dynamics. bioRxiv.","DOI":"10.2139\/ssrn.4529645"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.biopsych.2015.09.020","article-title":"Neuron-Targeted Caveolin-1 Improves Molecular Signaling, Plasticity, and Behavior Dependent on the Hippocampus in Adult and Aged Mice","volume":"81","author":"Mandyam","year":"2017","journal-title":"Biol. Psychiatry"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.1093\/cercor\/bhx196","article-title":"Neuron-Targeted Caveolin-1 Promotes Ultrastructural and Functional Hippocampal Synaptic Plasticity","volume":"28","author":"Egawa","year":"2018","journal-title":"Cereb. Cortex"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/s41392-025-02258-z","article-title":"Neuron-targeted caveolin-1 overexpression attenuates cognitive loss and pathological transcriptome changes in symptomatic Alzheimer\u2019s disease models","volume":"10","author":"Wang","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"33310","DOI":"10.1074\/jbc.M111.255976","article-title":"Neuron-targeted caveolin-1 protein enhances signaling and promotes arborization of primary neurons","volume":"286","author":"Head","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1124\/mol.105.012732","article-title":"Roscovitine triggers excitotoxicity in cultured granule neurons by enhancing glutamate release","volume":"68","author":"Monaco","year":"2005","journal-title":"Mol. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"173","DOI":"10.4103\/ijp.IJP_81_17","article-title":"Alteration in memory cognition due to activation of caveolin-1 and oxidative damage in a model of dementia of Alzheimer\u2019s type","volume":"51","author":"Gupta","year":"2019","journal-title":"Indian J. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1113\/jphysiol.2014.288209","article-title":"Cholesterol modulates open probability and desensitization of NMDA receptors","volume":"593","author":"Korinek","year":"2015","journal-title":"J. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1085\/jgp.200810043","article-title":"Nitric oxide-mediated modulation of synaptic activity by astrocytic P2Y receptors","volume":"132","author":"Mehta","year":"2008","journal-title":"J. Gen. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"140582","DOI":"10.1016\/j.jhazmat.2025.140582","article-title":"Lead exposure during development alters synaptic organization and protein expression in rat hippocampus","volume":"500","author":"Shirke","year":"2025","journal-title":"J. Hazard Mater."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/0197-0186(94)90096-5","article-title":"Cytotoxic effects of glutamic acid on PC12 cells","volume":"24","author":"Froissard","year":"1994","journal-title":"Neurochem. Int."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5637\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:50:22Z","timestamp":1782435022000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5637"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,22]]},"references-count":52,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27125637"],"URL":"https:\/\/doi.org\/10.3390\/ijms27125637","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,22]]}}}