{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T01:35:27Z","timestamp":1785893727580,"version":"3.56.0"},"reference-count":72,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004047","name":"Karolinska Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell. Mol. Life Sci."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Parechovirus ahumpari 3 (HPeV-3)<\/jats:italic>\n                    is among the main agents causing severe neonatal neurological infections such as encephalitis and meningitis. However, the underlying molecular mechanisms and changes to the host cellular landscape leading to neurological disease has been understudied. Through quantitative proteomic analysis of HPeV-3 infected neural organoids, we identified unique metabolic changes following HPeV-3 infection that indicate immunometabolic dysregulation. Protein and pathway analyses showed significant alterations in neurotransmission and potentially, neuronal excitotoxicity. Elevated levels of extracellular glutamate, lactate dehydrogenase (LDH), and neurofilament light (NfL) confirmed glutamate excitotoxicity to be a key mechanism contributing to neuronal toxicity in HPeV-3 infection and can lead to apoptosis induced by caspase signaling. These insights are pivotal in delineating the metabolic landscape following severe HPeV-3 CNS infection and may identify potential host targets for therapeutic interventions.\n                  <\/jats:p>","DOI":"10.1007\/s00018-025-05926-z","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T14:00:58Z","timestamp":1762351258000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Parechovirus-3 infection disrupts immunometabolism and leads to glutamate excitotoxicity in neural organoids"],"prefix":"10.1007","volume":"82","author":[{"given":"Pamela E.","family":"Capendale","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anoop T.","family":"Ambikan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e9s","family":"Garc\u00eda-Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata Vieira","family":"de S\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dasja","family":"Pajkrt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja C.","family":"Wolthers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ujjwal","family":"Neogi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2986-4884","authenticated-orcid":false,"given":"Adithya","family":"Sridhar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"issue":"1","key":"5926_CR1","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s12915-019-0678-9","volume":"17","author":"SK Thaker","year":"2019","unstructured":"Thaker SK, Ch\u2019ng J, Christofk HR (2019) Viral hijacking of cellular metabolism. BMC Biol 17(1):59","journal-title":"BMC Biol"},{"key":"5926_CR2","doi-asserted-by":"crossref","unstructured":"Sanchez EL, Lagunoff M (2015) Viral activation of cellular metabolism. Virology. ;479\u2013480:609\u201318","DOI":"10.1016\/j.virol.2015.02.038"},{"key":"5926_CR3","doi-asserted-by":"publisher","DOI":"10.3390\/v14030602","author":"CNS Allen","year":"2022","unstructured":"Allen CNS, Arjona SP, Santerre M, Sawaya BE (2022) Hallmarks of metabolic reprogramming and their role in viral pathogenesis. Viruses. https:\/\/doi.org\/10.3390\/v14030602","journal-title":"Viruses"},{"key":"5926_CR4","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.copbio.2020.10.004","volume":"68","author":"J Thyrsted","year":"2021","unstructured":"Thyrsted J, Holm CK (2021) Virus-induced metabolic reprogramming and innate sensing hereof by the infected host. Curr Opin Biotechnol 68:44\u201350","journal-title":"Curr Opin Biotechnol"},{"issue":"10","key":"5926_CR5","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1038\/s42255-022-00652-3","volume":"4","author":"CS Palmer","year":"2022","unstructured":"Palmer CS (2022) Innate metabolic responses against viral infections. Nat Metab 4(10):1245\u20131259","journal-title":"Nat Metab"},{"issue":"1","key":"5926_CR6","doi-asserted-by":"publisher","first-page":"2532","DOI":"10.1038\/s41467-024-46634-9","volume":"15","author":"PE Capendale","year":"2024","unstructured":"Capendale PE, Garc\u00eda-Rodr\u00edguez I, Ambikan AT, Mulder LA, Depla JA, Freeze E et al (2024) Parechovirus infection in human brain organoids: host innate inflammatory response and not neuro-infectivity correlates to neurologic disease. Nat Commun 15(1):2532","journal-title":"Nat Commun"},{"issue":"10","key":"5926_CR7","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1038\/nrmicro1284","volume":"3","author":"JL Whitton","year":"2005","unstructured":"Whitton JL, Cornell CT, Feuer R (2005) Host and virus determinants of picornavirus pathogenesis and tropism. Nat Rev Microbiol 3(10):765\u2013776","journal-title":"Nat Rev Microbiol"},{"issue":"2","key":"5926_CR8","doi-asserted-by":"publisher","first-page":"e1011132","DOI":"10.1371\/journal.ppat.1011132","volume":"19","author":"H Liu","year":"2023","unstructured":"Liu H, Zhu Z, Xue Q, Yang F, Li Z, Xue Z et al (2023) Innate sensing of picornavirus infection involves cGAS-STING-mediated antiviral responses triggered by mitochondrial DNA release. PLoS Pathog 19(2):e1011132","journal-title":"PLoS Pathog"},{"issue":"1","key":"5926_CR9","doi-asserted-by":"publisher","first-page":"3669","DOI":"10.1038\/s41467-021-23925-z","volume":"12","author":"AN Michi","year":"2021","unstructured":"Michi AN, Yipp BG, Dufour A, Lopes F, Proud D (2021) PGC-1\u03b1 mediates a metabolic host defense response in human airway epithelium during rhinovirus infections. Nat Commun 12(1):3669","journal-title":"Nat Commun"},{"key":"5926_CR10","doi-asserted-by":"publisher","DOI":"10.3390\/cells9020473","author":"ML Cheng","year":"2020","unstructured":"Cheng ML, Chien KY, Lai CH, Li GJ, Lin JF, Ho HY (2020) Metabolic reprogramming of host cells in response to enteroviral infection. Cells. https:\/\/doi.org\/10.3390\/cells9020473","journal-title":"Cells"},{"key":"5926_CR11","doi-asserted-by":"crossref","unstructured":"Zou Z, Tsang JO, Yan B, Chik KK, Chan CC, Cao J et al (2020) Metabolic profiling reveals significant perturbations of intracellular glucose homeostasis in Enterovirus-Infected cells. Metabolites. ;10(8)","DOI":"10.3390\/metabo10080302"},{"key":"5926_CR12","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00396","author":"Y Fan","year":"2018","unstructured":"Fan Y, Sanyal S, Bruzzone R (2018) Breaking bad: how viruses subvert the cell cycle. Front Cell Infect Microbiol. https:\/\/doi.org\/10.3389\/fcimb.2018.00396","journal-title":"Front Cell Infect Microbiol"},{"key":"5926_CR13","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/978-1-4939-0888-2_10","volume":"1170","author":"S Bagga","year":"2014","unstructured":"Bagga S, Bouchard MJ (2014) Cell cycle regulation during viral infection. Methods Mol Biol 1170:165\u2013227","journal-title":"Methods Mol Biol"},{"issue":"8","key":"5926_CR14","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/S2352-4642(20)30181-4","volume":"4","author":"TMT van Hinsbergh","year":"2020","unstructured":"van Hinsbergh TMT, Elbers RG, Hans Ket JCF, van Furth AM, Obihara CC (2020) Neurological and neurodevelopmental outcomes after human parechovirus CNS infection in neonates and young children: a systematic review and meta-analysis. Lancet Child Adolesc Health 4(8):592\u2013605","journal-title":"Lancet Child Adolesc Health"},{"issue":"8","key":"5926_CR15","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1212\/01.wnl.0000208429.69676.23","volume":"66","author":"M Verboon-Maciolek","year":"2006","unstructured":"Verboon-Maciolek M, Groenendaal F, Cowan F, Govaert P, Van Loon A, De Vries L (2006) White matter damage in neonatal enterovirus meningoencephalitis. Neurology 66(8):1267\u20131269","journal-title":"Neurology"},{"key":"5926_CR16","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2015-2848","author":"PN Britton","year":"2016","unstructured":"Britton PN, Dale RC, Nissen MD, Crawford N, Elliott E, Macartney K et al (2016) Parechovirus encephalitis and neurodevelopmental outcomes. Pediatrics. https:\/\/doi.org\/10.1542\/peds.2015-2848","journal-title":"Pediatrics"},{"key":"5926_CR17","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1007\/s00431-014-2483-3","volume":"174","author":"S Vergnano","year":"2015","unstructured":"Vergnano S, Kadambari S, Whalley K, Menson EN, Martinez-Alier N, Cooper M et al (2015) Characteristics and outcomes of human parechovirus infection in infants (2008\u20132012). Eur J Pediatr 174:919\u2013924","journal-title":"Eur J Pediatr"},{"issue":"2","key":"5926_CR18","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1086\/498905","volume":"42","author":"KSM Benschop","year":"2006","unstructured":"Benschop KSM, Schinkel J, Minnaar RP, Pajkrt D, Spanjerberg L, Kraakman HC et al (2006) Human parechovirus infections in Dutch children and the association between serotype and disease severity. Clin Infect Dis 42(2):204\u2013210","journal-title":"Clin Infect Dis"},{"key":"5926_CR19","doi-asserted-by":"crossref","unstructured":"Uhl\u00e9n M, Fagerberg L, Hallstr\u00f6m BM, Lindskog C, Oksvold P, Mardinoglu A et al (2015)\u00a0Proteomics. Tissue-based map of the human proteome. Science 347(6220):1260419","DOI":"10.1126\/science.1260419"},{"key":"5926_CR20","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1126\/scisignal.aaz1482","volume":"13","author":"JL Robinson","year":"2020","unstructured":"Robinson JL, Kocaba\u015f P, Wang H, Cholley PE, Cook D, Nilsson A et al (2020) An atlas of human metabolism. Sci Signal 13:624","journal-title":"Sci Signal"},{"issue":"5134","key":"5926_CR21","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1126\/science.7901908","volume":"262","author":"JT Coyle","year":"1993","unstructured":"Coyle JT, Puttfarcken P (1993) Oxidative stress, glutamate, and neurodegenerative disorders. Science 262(5134):689\u2013695","journal-title":"Science"},{"issue":"11\u201312","key":"5926_CR22","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1016\/j.bbadis.2006.05.002","volume":"1762","author":"L Van Den Bosch","year":"2006","unstructured":"Van Den Bosch L, Van Damme P, Bogaert E, Robberecht W (2006) The role of excitotoxicity in the pathogenesis of amyotrophic lateral sclerosis. Biochim Biophys Acta 1762(11\u201312):1068\u20131082","journal-title":"Biochim Biophys Acta"},{"key":"5926_CR23","doi-asserted-by":"crossref","unstructured":"Cowan CM, Raymond LA (2006) Selective Neuronal Degeneration in Huntington\u2019s Disease. Current Topics in Developmental Biology. 75: Academic Press; pp. 25\u201371","DOI":"10.1016\/S0070-2153(06)75002-5"},{"issue":"1","key":"5926_CR24","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1515\/revneuro-2012-0062","volume":"24","author":"M Kostic","year":"2013","unstructured":"Kostic M, Zivkovic N, Stojanovic I (2013) Multiple sclerosis and glutamate excitotoxicity. Rev Neurosci 24(1):71\u201388","journal-title":"Rev Neurosci"},{"key":"5926_CR25","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.00261","author":"AM Gorska","year":"2020","unstructured":"Gorska AM, Eugenin EA (2020) The glutamate system as a crucial regulator of CNS toxicity and survival of HIV reservoirs. Front Cell Infect Microbiol. https:\/\/doi.org\/10.3389\/fcimb.2020.00261","journal-title":"Front Cell Infect Microbiol"},{"issue":"1","key":"5926_CR26","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1002\/glia.23895","volume":"69","author":"DD Li Puma","year":"2021","unstructured":"Li Puma DD, Marcocci ME, Lazzarino G, De Chiara G, Tavazzi B, Palamara AT et al (2021) Ca(2+) -dependent release of ATP from astrocytes affects herpes simplex virus type 1 infection of neurons. Glia 69(1):201\u2013215","journal-title":"Glia"},{"issue":"5","key":"5926_CR27","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1002\/jmri.22366","volume":"32","author":"T Ernst","year":"2010","unstructured":"Ernst T, Jiang CS, Nakama H, Buchthal S, Chang L (2010) Lower brain glutamate is associated with cognitive deficits in HIV patients: a new mechanism for HIV-associated neurocognitive disorder. J Magn Reson Imaging 32(5):1045\u20131053","journal-title":"J Magn Reson Imaging"},{"issue":"18","key":"5926_CR28","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1212\/WNL.0000000000000932","volume":"83","author":"AC Young","year":"2014","unstructured":"Young AC, Yiannoutsos CT, Hegde M, Lee E, Peterson J, Walter R et al (2014) Cerebral metabolite changes prior to and after antiretroviral therapy in primary HIV infection. Neurology 83(18):1592\u20131600","journal-title":"Neurology"},{"issue":"6","key":"5926_CR29","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1007\/BF03210849","volume":"16","author":"RA Cohen","year":"2010","unstructured":"Cohen RA, Harezlak J, Gongvatana A, Buchthal S, Schifitto G, Clark U et al (2010) Cerebral metabolite abnormalities in human immunodeficiency virus are associated with cortical and subcortical volumes. J Neurovirol 16(6):435\u2013444","journal-title":"J Neurovirol"},{"issue":"1","key":"5926_CR30","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa M, Goto S (2000) KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28(1):27\u201330","journal-title":"Nucleic Acids Res"},{"issue":"32","key":"5926_CR31","doi-asserted-by":"publisher","first-page":"53791","DOI":"10.18632\/oncotarget.17339","volume":"8","author":"H Wang","year":"2017","unstructured":"Wang H, Farhan M, Xu J, Lazarovici P, Zheng W (2017) The involvement of DARPP-32 in the pathophysiology of schizophrenia. Oncotarget 8(32):53791\u201353803","journal-title":"Oncotarget"},{"issue":"8","key":"5926_CR32","doi-asserted-by":"publisher","first-page":"102899","DOI":"10.1016\/j.isci.2021.102899","volume":"24","author":"YJ Park","year":"2021","unstructured":"Park YJ, Kim S, Shim HP, Park JH, Lee G, Kim TY et al (2021) Phosphatidylserine synthase plays an essential role in glia and affects development, as well as the maintenance of neuronal function. iScience 24(8):102899","journal-title":"iScience"},{"key":"5926_CR33","doi-asserted-by":"publisher","first-page":"975176","DOI":"10.3389\/fnagi.2022.975176","volume":"14","author":"X Ma","year":"2022","unstructured":"Ma X, Li X, Wang W, Zhang M, Yang B, Miao Z (2022) Phosphatidylserine, inflammation, and central nervous system diseases. Front Aging Neurosci 14:975176","journal-title":"Front Aging Neurosci"},{"key":"5926_CR34","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.jbior.2015.11.003","volume":"61","author":"YR Yang","year":"2016","unstructured":"Yang YR, Kang D-S, Lee C, Seok H, Follo MY, Cocco L et al (2016) Primary phospholipase c and brain disorders. Adv Biol Regul 61:80\u201385","journal-title":"Adv Biol Regul"},{"issue":"1","key":"5926_CR35","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.jbior.2012.09.008","volume":"53","author":"H-J Jang","year":"2013","unstructured":"Jang H-J, Yang YR, Kim JK, Choi JH, Seo Y-K, Lee YH (2013) Phospholipase C-\u03b31 involved in brain disorders. Adv Biol Regul 53(1):51\u201362","journal-title":"Adv Biol Regul"},{"issue":"15","key":"5926_CR36","doi-asserted-by":"publisher","first-page":"3840","DOI":"10.1523\/JNEUROSCI.2031-17.2018","volume":"38","author":"J Chen","year":"2018","unstructured":"Chen J, Van Gulden S, McGuire TL, Fleming AC, Oka C, Kessler JA et al (2018) BMP-responsive protease HtrA1 is differentially expressed in astrocytes and regulates astrocytic development and injury response. J Neurosci 38(15):3840\u20133857","journal-title":"J Neurosci"},{"issue":"1","key":"5926_CR37","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-021-00426-7","volume":"16","author":"F Chen","year":"2021","unstructured":"Chen F, Swartzlander DB, Ghosh A, Fryer JD, Wang B, Zheng H (2021) Clusterin secreted from astrocyte promotes excitatory synaptic transmission and ameliorates Alzheimer\u2019s disease neuropathology. Mol Neurodegener 16(1):5","journal-title":"Mol Neurodegener"},{"issue":"3","key":"5926_CR38","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1086\/589752","volume":"47","author":"KC Wolthers","year":"2008","unstructured":"Wolthers KC, Benschop KS, Schinkel J, Molenkamp R, Bergevoet RM, Spijkerman IJ et al (2008) Human parechoviruses as an important viral cause of sepsislike illness and meningitis in young children. Clin Infect Dis 47(3):358\u2013363","journal-title":"Clin Infect Dis"},{"issue":"3","key":"5926_CR39","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1007\/s13311-019-00755-y","volume":"16","author":"JC Ryu","year":"2019","unstructured":"Ryu JC, Zimmer ER, Rosa-Neto P, Yoon SO (2019) Consequences of metabolic disruption in Alzheimer\u2019s disease pathology. Neurotherapeutics 16(3):600\u2013610","journal-title":"Neurotherapeutics"},{"issue":"1","key":"5926_CR40","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1186\/s12974-023-02898-4","volume":"20","author":"M Dobrzy\u0144ska","year":"2023","unstructured":"Dobrzy\u0144ska M, Moniuszko-Malinowska A, Skrzydlewska E (2023) Metabolic response to CNS infection with flaviviruses. J Neuroinflammation 20(1):218","journal-title":"J Neuroinflammation"},{"issue":"6","key":"5926_CR41","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1016\/j.cmet.2011.08.016","volume":"14","author":"M B\u00e9langer","year":"2011","unstructured":"B\u00e9langer M, Allaman I, Magistretti Pierre J (2011) Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab 14(6):724\u2013738","journal-title":"Cell Metab"},{"key":"5926_CR42","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.conb.2017.09.012","volume":"47","author":"R Nortley","year":"2017","unstructured":"Nortley R, Attwell D (2017) Control of brain energy supply by astrocytes. Curr Opin Neurobiol 47:80\u201385","journal-title":"Curr Opin Neurobiol"},{"issue":"1","key":"5926_CR43","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/S0165-0173(00)00038-2","volume":"34","author":"A Ames","year":"2000","unstructured":"Ames A (2000) CNS energy metabolism as related to function. Brain Res Rev 34(1):42\u201368","journal-title":"Brain Res Rev"},{"issue":"4","key":"5926_CR44","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1002\/mrdd.1032","volume":"7","author":"MV Johnston","year":"2001","unstructured":"Johnston MV (2001) Excitotoxicity in neonatal hypoxia. Ment Retard Dev Disabil Res Rev 7(4):229\u2013234","journal-title":"Ment Retard Dev Disabil Res Rev"},{"issue":"5","key":"5926_CR45","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1002\/ana.22419","volume":"69","author":"FJ Northington","year":"2011","unstructured":"Northington FJ, Chavez-Valdez R, Martin LJ (2011) Neuronal cell death in neonatal hypoxia-ischemia. Ann Neurol 69(5):743\u2013758","journal-title":"Ann Neurol"},{"key":"5926_CR46","doi-asserted-by":"publisher","first-page":"753683","DOI":"10.3389\/fimmu.2021.753683","volume":"12","author":"MW Jan","year":"2021","unstructured":"Jan MW, Su HL, Chang TH, Tsai KJ (2021) Characterization of pathogenesis and inflammatory responses to experimental parechovirus encephalitis. Front Immunol 12:753683","journal-title":"Front Immunol"},{"issue":"8","key":"5926_CR47","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.1097\/00001756-199906030-00030","volume":"10","author":"P Strocchi","year":"1999","unstructured":"Strocchi P, Rauzi F, Cevolani D (1999) Neuronal loss up-regulates clusterin mRNA in living neurons and glial cells in the rat brain. Neuroreport 10(8):1789\u20131792","journal-title":"Neuroreport"},{"issue":"3","key":"5926_CR48","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1046\/j.1523-1747.1999.00531.x","volume":"112","author":"I Viard","year":"1999","unstructured":"Viard I, Wehrli P, Jornot L, Bullani R, Vechietti J-L, French LE et al (1999) Clusterin gene expression mediates resistance to apoptotic cell death induced by heat shock and oxidative stress. J Invest Dermatol 112(3):290\u2013296","journal-title":"J Invest Dermatol"},{"issue":"1\u20132","key":"5926_CR49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.mam.2008.08.006","volume":"30","author":"HJ Forman","year":"2009","unstructured":"Forman HJ, Zhang H, Rinna A (2009) Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med 30(1\u20132):1\u201312","journal-title":"Mol Aspects Med"},{"issue":"7","key":"5926_CR50","doi-asserted-by":"publisher","first-page":"2701","DOI":"10.1073\/pnas.1817885116","volume":"116","author":"TW Sedlak","year":"2019","unstructured":"Sedlak TW, Paul BD, Parker GM, Hester LD, Snowman AM, Taniguchi Y et al (2019) The glutathione cycle shapes synaptic glutamate activity. Proc Natl Acad Sci U S A 116(7):2701\u20132706","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"5926_CR51","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11129-5","volume":"10","author":"Z-x Cheng","year":"2019","unstructured":"Cheng Z-x, Guo C, Chen Z-g, Yang T-c, Zhang J-y, Wang J et al (2019) Glycine, serine and threonine metabolism confounds efficacy of complement-mediated killing. Nat Commun 10(1):3325","journal-title":"Nat Commun"},{"key":"5926_CR52","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102512","volume":"58","author":"TS Kou","year":"2022","unstructured":"Kou TS, Wu JH, Chen XW, Chen ZG, Zheng J, Peng B (2022) Exogenous glycine promotes oxidation of glutathione and restores sensitivity of bacterial pathogens to serum-induced cell death. Redox Biol 58:102512","journal-title":"Redox Biol"},{"key":"5926_CR53","doi-asserted-by":"publisher","first-page":"725043","DOI":"10.3389\/fcimb.2021.725043","volume":"11","author":"FJ S\u00e1nchez-Garc\u00eda","year":"2021","unstructured":"S\u00e1nchez-Garc\u00eda FJ, P\u00e9rez-Hern\u00e1ndez CA, Rodr\u00edguez-Murillo M, Moreno-Altamirano MMB (2021) The role of tricarboxylic acid cycle metabolites in viral infections. Front Cell Infect Microbiol 11:725043","journal-title":"Front Cell Infect Microbiol"},{"issue":"8","key":"5926_CR54","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1016\/j.cmet.2021.07.006","volume":"33","author":"G Bonvento","year":"2021","unstructured":"Bonvento G, Bola\u00f1os JP (2021) Astrocyte-neuron metabolic cooperation shapes brain activity. Cell Metab 33(8):1546\u20131564","journal-title":"Cell Metab"},{"key":"5926_CR55","doi-asserted-by":"crossref","unstructured":"McHale-Owen H, Faller KME, Chaytow H, Gillingwater TH (2025) Phosphoglycerate kinase 1 as a therapeutic target in neurological disease. Trends Mol Med","DOI":"10.1016\/j.molmed.2025.03.008"},{"key":"5926_CR56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neubiorev.2016.05.006","volume":"68","author":"MK Jha","year":"2016","unstructured":"Jha MK, Lee I-K, Suk K (2016) Metabolic reprogramming by the pyruvate dehydrogenase kinase\u2013lactic acid axis: linking metabolism and diverse neuropathophysiologies. Neurosci Biobehav Rev 68:1\u201319","journal-title":"Neurosci Biobehav Rev"},{"key":"5926_CR57","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1007\/978-3-319-45096-4_13","volume":"13","author":"AR Jayakumar","year":"2016","unstructured":"Jayakumar AR, Norenberg MD (2016) Glutamine synthetase: role in neurological disorders. Adv Neurobiol 13:327\u2013350","journal-title":"Adv Neurobiol"},{"issue":"2","key":"5926_CR58","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/S0197-0186(02)00033-5","volume":"41","author":"I Su\u00e1rez","year":"2002","unstructured":"Su\u00e1rez I, Bodega G, Fern\u00e1ndez B (2002) Glutamine synthetase in brain: effect of ammonia. Neurochem Int 41(2):123\u2013142","journal-title":"Neurochem Int"},{"issue":"7","key":"5926_CR59","doi-asserted-by":"publisher","first-page":"2214","DOI":"10.1523\/JNEUROSCI.07-07-02214.1987","volume":"7","author":"C Aoki","year":"1987","unstructured":"Aoki C, Milner TA, Sheu K-F, Blass JP, Pickel VM (1987) Regional distribution of astrocytes with intense immunoreactivity for glutamate dehydrogenase in rat brain: implications for neuron-glia interactions in glutamate transmission. J Neurosci 7(7):2214\u20132231","journal-title":"J Neurosci"},{"issue":"1","key":"5926_CR60","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3390\/biology6010011","volume":"6","author":"A Plaitakis","year":"2017","unstructured":"Plaitakis A, Kalef-Ezra E, Kotzamani D, Zaganas I, Spanaki C (2017) The glutamate dehydrogenase pathway and its roles in cell and tissue biology in health and disease. Biology 6(1):11","journal-title":"Biology"},{"issue":"1","key":"5926_CR61","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/s41398-023-02534-y","volume":"13","author":"K Asraf","year":"2023","unstructured":"Asraf K, Zaidan H, Natoor B, Gaisler-Salomon I (2023) Synergistic, long-term effects of glutamate dehydrogenase 1 deficiency and mild stress on cognitive function and mPFC gene and miRNA expression. Transl Psychiatry 13(1):248","journal-title":"Transl Psychiatry"},{"issue":"8","key":"5926_CR62","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1016\/j.cmi.2020.09.031","volume":"27","author":"G Westman","year":"2021","unstructured":"Westman G, Aurelius E, Ahlm C, Blennow K, Eriksson K, Lind L et al (2021) Cerebrospinal fluid biomarkers of brain injury, inflammation and synaptic autoimmunity predict long-term neurocognitive outcome in herpes simplex encephalitis. Clin Microbiol Infect 27(8):1131\u20131136","journal-title":"Clin Microbiol Infect"},{"issue":"5","key":"5926_CR63","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1007\/s13365-020-00889-2","volume":"26","author":"T Tyrberg","year":"2020","unstructured":"Tyrberg T, Nilsson S, Blennow K, Zetterberg H, Grahn A (2020) Serum and cerebrospinal fluid neurofilament light chain in patients with central nervous system infections caused by varicella-zoster virus. J Neurovirol 26(5):719\u2013726","journal-title":"J Neurovirol"},{"issue":"9","key":"5926_CR64","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1080\/23744235.2024.2345712","volume":"56","author":"K Als\u00e9n","year":"2024","unstructured":"Als\u00e9n K, Patzi Churqui M, Norder H, Rembeck K, Zetterberg H, Blennow K et al (2024) Biomarkers and genotypes in patients with central nervous system infection caused by enterovirus. Infectious Diseases 56(9):722\u2013731","journal-title":"Infectious Diseases"},{"key":"5926_CR65","volume":"7","author":"CDM Fulton","year":"2020","unstructured":"Fulton CDM, Beasley DWC, Bente DA, Dineley KT (2020) Long-term, West Nile virus-induced neurological changes: a comparison of patients and rodent models. Brain Behav Immun 7:100105","journal-title":"Brain Behav Immun"},{"issue":"5","key":"5926_CR66","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.cnr.2006.09.009","volume":"6","author":"NB Erdmann","year":"2006","unstructured":"Erdmann NB, Whitney NP, Zheng J (2006) Potentiation of excitotoxicity in HIV-1 associated dementia and the significance of glutaminase. Clin Neurosci Res 6(5):315\u2013328","journal-title":"Clin Neurosci Res"},{"key":"5926_CR67","doi-asserted-by":"crossref","unstructured":"Chaganti J, Poudel G, Cysique LA, Dore GJ, Kelleher A, Matthews G et al (2024) Blood brain barrier disruption and glutamatergic excitotoxicity in post-acute sequelae of SARS COV-2 infection cognitive impairment: potential biomarkers and a window into pathogenesis. Front Neurol. ;15","DOI":"10.3389\/fneur.2024.1350848"},{"key":"5926_CR68","first-page":"493","volume":"27","author":"R Lj","year":"1938","unstructured":"Lj R (1938) A simple method of estimating Fifty per cent endpoints. Am J Hyg 27:493\u2013495","journal-title":"Am J Hyg"},{"issue":"7","key":"5926_CR69","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W et al (2015) Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 43(7):e47","journal-title":"Nucleic Acids Res"},{"issue":"8","key":"5926_CR70","doi-asserted-by":"publisher","first-page":"4378","DOI":"10.1093\/nar\/gkt111","volume":"41","author":"L V\u00e4remo","year":"2013","unstructured":"V\u00e4remo L, Nielsen J, Nookaew I (2013) Enriching the gene set analysis of genome-wide data by incorporating directionality of gene expression and combining statistical hypotheses and methods. Nucleic Acids Res 41(8):4378\u20134391","journal-title":"Nucleic Acids Res"},{"issue":"18","key":"5926_CR71","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","volume":"32","author":"Z Gu","year":"2016","unstructured":"Gu Z, Eils R, Schlesner M (2016) Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics 32(18):2847\u20132849","journal-title":"Bioinformatics"},{"issue":"10","key":"5926_CR72","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1515\/cclm-2015-1195","volume":"54","author":"J Kuhle","year":"2016","unstructured":"Kuhle J, Barro C, Andreasson U, Derfuss T, Lindberg R, Sandelius \u00c5 et al (2016) Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa. Clin Chem Lab Med (CCLM) 54(10):1655\u20131661","journal-title":"Clin Chem Lab Med (CCLM)"}],"container-title":["Cellular and Molecular Life Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00018-025-05926-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00018-025-05926-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00018-025-05926-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T15:03:50Z","timestamp":1762355030000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00018-025-05926-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,5]]},"references-count":72,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["5926"],"URL":"https:\/\/doi.org\/10.1007\/s00018-025-05926-z","relation":{},"ISSN":["1420-9071"],"issn-type":[{"value":"1420-9071","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,5]]},"assertion":[{"value":"9 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 August 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 September 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 November 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"382"}}