{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:01:49Z","timestamp":1790834509923,"version":"4.1.0"},"reference-count":94,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T00:00:00Z","timestamp":1658188800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T00:00:00Z","timestamp":1658188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006510","name":"ARSLA","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006510","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007379","name":"Fondation pour l'Aide \u00e0 la Recherche sur la Scl\u00e9rose en Plaques","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007379","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ANR","award":["ANR-20-CE17-001"],"award-info":[{"award-number":["ANR-20-CE17-001"]}]},{"name":"GPR BRAIN_2030"},{"name":"LabEx DISTALZ"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell. Mol. Life Sci."],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Amyotrophic lateral sclerosis (ALS) is a fatal motoneuron (MN) disease characterized by protein misfolding and aggregation leading to cellular degeneration. So far neither biomarker, nor effective treatment has been found. ATP signaling and P2X4 receptors (P2X4) are upregulated in various neurodegenerative diseases. Here we show that several ALS-related misfolded proteins including mutants of SOD1 or TDP-43 lead to a significant increase in surface P2X4 receptor density and function in vitro. In addition, we demonstrate in the spinal the cord of SOD1-G93A (SOD1) mice that misfolded SOD1-G93A proteins directly interact with endocytic adaptor protein-2 (AP2); thus, acting as negative competitors for the interaction between AP2 and P2X4, impairing constitutive P2X4 endocytosis. The higher P2X4 surface density was particularly observed in peripheral macrophages of SOD1 mice before the onset and during the progression of ALS symptoms positioning P2X4 as a potential early biomarker for ALS. P2X4 expression was also upregulated in spinal microglia of SOD1 mice during ALS and affect microglial inflammatory responses. Importantly, we report using double transgenic SOD1 mice expressing internalization-defective P2X4mCherryIN knock-in gene or invalidated for the P2X4 gene that P2X4 is instrumental for motor symptoms, ALS progression and survival. This study highlights the role of P2X4 in the pathophysiology of ALS and thus its potential for the development of biomarkers and treatments. We also decipher the molecular mechanism by which misfolded proteins related to ALS impact P2X4 trafficking at early pathological stage in cells expressing-P2X4.<\/jats:p>","DOI":"10.1007\/s00018-022-04461-5","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T07:03:08Z","timestamp":1658214188000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Increased surface P2X4 receptors by mutant SOD1 proteins contribute to ALS pathogenesis in SOD1-G93A mice"],"prefix":"10.1007","volume":"79","author":[{"given":"El\u00e9onore","family":"Bertin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Fayoux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Carracedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre-Olivier","family":"Fernagut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich","family":"Koch-Nolte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Blum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine S.","family":"Bertrand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2187-9037","authenticated-orcid":false,"given":"Eric","family":"Bou\u00e9-Grabot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,19]]},"reference":[{"key":"4461_CR1","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1038\/35097565","volume":"2","author":"DW Cleveland","year":"2001","unstructured":"Cleveland DW, Rothstein JD (2001) From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nat Rev Neurosci 2:806\u2013819","journal-title":"Nat Rev Neurosci"},{"key":"4461_CR2","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.1126\/science.1154584","volume":"319","author":"J Sreedharan","year":"2008","unstructured":"Sreedharan J, Blair IP, Tripathi VB, Hu X, Vance C, Rogelj B, Ackerley S, Durnall JC, Williams KL, Buratti E et al (2008) TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319:1668\u20131672","journal-title":"Science"},{"key":"4461_CR3","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1126\/science.1166066","volume":"323","author":"TJ Kwiatkowski Jr","year":"2009","unstructured":"Kwiatkowski TJ Jr, Bosco DA, Leclerc AL, Tamrazian E, Vanderburg CR, Russ C, Davis A, Gilchrist J, Kasarskis EJ, Munsat T et al (2009) Mutations in the FUS\/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323:1205\u20131208","journal-title":"Science"},{"key":"4461_CR4","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.neuron.2011.09.010","volume":"72","author":"AE Renton","year":"2011","unstructured":"Renton AE, Majounie E, Waite A, Simon-Sanchez J, Rollinson S, Gibbs JR, Schymick JC, Laaksovirta H, van Swieten JC, Myllykangas L et al (2011) A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72:257\u2013268","journal-title":"Neuron"},{"key":"4461_CR5","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1126\/science.1134108","volume":"314","author":"M Neumann","year":"2006","unstructured":"Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM et al (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314:130\u2013133","journal-title":"Science"},{"key":"4461_CR6","doi-asserted-by":"publisher","first-page":"33","DOI":"10.4161\/pri.27602","volume":"8","author":"LI Grad","year":"2014","unstructured":"Grad LI, Cashman NR (2014) Prion-like activity of Cu\/Zn superoxide dismutase: implications for amyotrophic lateral sclerosis. Prion 8:33\u201341","journal-title":"Prion"},{"key":"4461_CR7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035050","volume":"7","author":"E Pokrishevsky","year":"2012","unstructured":"Pokrishevsky E, Grad LI, Yousefi M, Wang J, Mackenzie IR, Cashman NR (2012) Aberrant localization of FUS and TDP43 is associated with misfolding of SOD1 in amyotrophic lateral sclerosis. PLoS ONE 7:e35050","journal-title":"PLoS ONE"},{"key":"4461_CR8","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1007\/s13311-014-0329-3","volume":"12","author":"KG Hooten","year":"2015","unstructured":"Hooten KG, Beers DR, Zhao W, Appel SH (2015) Protective and toxic neuroinflammation in amyotrophic lateral sclerosis. Neurotherapeutics 12:364\u2013375","journal-title":"Neurotherapeutics"},{"key":"4461_CR9","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1038\/s41593-020-00718-z","volume":"23","author":"A Chiot","year":"2020","unstructured":"Chiot A, Zaidi S, Iltis C, Ribon M, Berriat F, Schiaffino L, Jolly A, de la Grange P, Mallat M, Bohl D et al (2020) Modifying macrophages at the periphery has the capacity to change microglial reactivity and to extend ALS survival. Nat Neurosci 23:1339\u20131351","journal-title":"Nat Neurosci"},{"key":"4461_CR10","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1097\/WCO.0000000000000729","volume":"32","author":"A Chiot","year":"2019","unstructured":"Chiot A, Lobsiger CS, Boillee S (2019) New insights on the disease contribution of neuroinflammation in amyotrophic lateral sclerosis. Curr Opin Neurol 32:764\u2013770","journal-title":"Curr Opin Neurol"},{"key":"4461_CR11","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.neuropharm.2015.10.026","volume":"104","author":"C Volonte","year":"2016","unstructured":"Volonte C, Apolloni S, Parisi C, Amadio S (2016) Purinergic contribution to amyotrophic lateral sclerosis. Neuropharmacology 104:180\u2013193","journal-title":"Neuropharmacology"},{"key":"4461_CR12","doi-asserted-by":"publisher","first-page":"403","DOI":"10.2174\/1568007033482643","volume":"2","author":"C Volonte","year":"2003","unstructured":"Volonte C, Amadio S, Cavaliere F, D\u2019Ambrosi N, Vacca F, Bernardi G (2003) Extracellular ATP and neurodegeneration. Curr Drug Targets CNS Neurol Disord 2:403\u2013412","journal-title":"Curr Drug Targets CNS Neurol Disord"},{"key":"4461_CR13","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.pharmthera.2011.06.002","volume":"132","author":"C Volonte","year":"2011","unstructured":"Volonte C, Apolloni S, Carri MT, D\u2019Ambrosi N (2011) ALS: focus on purinergic signalling. Pharmacol Ther 132:111\u2013122","journal-title":"Pharmacol Ther"},{"key":"4461_CR14","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/nrd2605","volume":"7","author":"G Burnstock","year":"2008","unstructured":"Burnstock G (2008) Purinergic signalling and disorders of the central nervous system. Nat Rev Drug Discov 7:575\u2013590","journal-title":"Nat Rev Drug Discov"},{"key":"4461_CR15","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.neuropharm.2015.05.031","volume":"104","author":"G Burnstock","year":"2016","unstructured":"Burnstock G (2016) An introduction to the roles of purinergic signalling in neurodegeneration, neuroprotection and neuroregeneration. Neuropharmacology 104:4\u201317","journal-title":"Neuropharmacology"},{"key":"4461_CR16","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.brainresbull.2018.10.014","volume":"151","author":"L Erb","year":"2019","unstructured":"Erb L, Woods LT, Khalafalla MG, Weisman GA (2019) Purinergic signaling in Alzheimer\u2019s disease. Brain Res Bull 151:25\u201337","journal-title":"Brain Res Bull"},{"key":"4461_CR17","doi-asserted-by":"publisher","first-page":"2413","DOI":"10.1007\/s11064-019-02798-1","volume":"44","author":"A Toth","year":"2019","unstructured":"Toth A, Antal Z, Bereczki D, Sperlagh B (2019) Purinergic signalling in Parkinson\u2019s disease: a multi-target system to combat neurodegeneration. Neurochem Res 44:2413\u20132422","journal-title":"Neurochem Res"},{"key":"4461_CR18","doi-asserted-by":"publisher","first-page":"257","DOI":"10.2174\/1871527315666160922104848","volume":"16","author":"G Burnstock","year":"2017","unstructured":"Burnstock G (2017) Purinergic Signalling and Neurological Diseases: An Update. CNS Neurol Disord Drug Targets 16:257\u2013265","journal-title":"CNS Neurol Disord Drug Targets"},{"key":"4461_CR19","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1016\/S0025-7753(08)75506-4","volume":"131","author":"RA Cunha","year":"2008","unstructured":"Cunha RA (2008) Caffeine, adenosine receptors, memory and Alzheimer disease. Med Clin (Barc) 131:790\u2013795","journal-title":"Med Clin (Barc)"},{"key":"4461_CR20","doi-asserted-by":"publisher","first-page":"14741","DOI":"10.1523\/JNEUROSCI.3728-09.2009","volume":"29","author":"PM Canas","year":"2009","unstructured":"Canas PM, Porciuncula LO, Cunha GM, Silva CG, Machado NJ, Oliveira JM, Oliveira CR, Cunha RA (2009) Adenosine A2A receptor blockade prevents synaptotoxicity and memory dysfunction caused by beta-amyloid peptides via p38 mitogen-activated protein kinase pathway. J Neurosci 29:14741\u201314751","journal-title":"J Neurosci"},{"key":"4461_CR21","doi-asserted-by":"publisher","first-page":"9452","DOI":"10.1038\/s41598-017-10147-x","volume":"7","author":"X Morato","year":"2017","unstructured":"Morato X, Lujan R, Lopez-Cano M, Gandia J, Stagljar I, Watanabe M, Cunha RA, Fernandez-Duenas V, Ciruela F (2017) The Parkinson\u2019s disease-associated GPR37 receptor interacts with striatal adenosine A2A receptor controlling its cell surface expression and function in vivo. Sci Rep 7:9452","journal-title":"Sci Rep"},{"key":"4461_CR22","doi-asserted-by":"publisher","first-page":"3636","DOI":"10.1093\/brain\/awz288","volume":"142","author":"K Carvalho","year":"2019","unstructured":"Carvalho K, Faivre E, Pietrowski MJ, Marques X, Gomez-Murcia V, Deleau A, Huin V, Hansen JN, Kozlov S, Danis C et al (2019) Exacerbation of C1q dysregulation, synaptic loss and memory deficits in tau pathology linked to neuronal adenosine A2A receptor. Brain 142:3636\u20133654","journal-title":"Brain"},{"key":"4461_CR23","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.neuron.2014.06.005","volume":"83","author":"JT Pougnet","year":"2014","unstructured":"Pougnet JT, Toulme E, Martinez A, Choquet D, Hosy E, Boue-Grabot E (2014) ATP P2X receptors downregulate AMPA receptor trafficking and postsynaptic efficacy in hippocampal neurons. Neuron 83:417\u2013430","journal-title":"Neuron"},{"key":"4461_CR24","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.neuron.2012.09.024","volume":"76","author":"BS Khakh","year":"2012","unstructured":"Khakh BS, North RA (2012) Neuromodulation by extracellular ATP and P2X receptors in the CNS. Neuron 76:51\u201369","journal-title":"Neuron"},{"key":"4461_CR25","doi-asserted-by":"publisher","first-page":"31836","DOI":"10.1038\/srep31836","volume":"6","author":"JT Pougnet","year":"2016","unstructured":"Pougnet JT, Compans B, Martinez A, Choquet D, Hosy E, Boue-Grabot E (2016) P2X-mediated AMPA receptor internalization and synaptic depression is controlled by two CaMKII phosphorylation sites on GluA1 in hippocampal neurons. Sci Rep 6:31836","journal-title":"Sci Rep"},{"key":"4461_CR26","doi-asserted-by":"publisher","first-page":"9454275","DOI":"10.1155\/2017\/9454275","volume":"2017","author":"E Boue-Grabot","year":"2017","unstructured":"Boue-Grabot E, Pankratov Y (2017) Modulation of central synapses by astrocyte-released ATP and postsynaptic P2X receptors. Neural Plast 2017:9454275","journal-title":"Neural Plast"},{"key":"4461_CR27","doi-asserted-by":"publisher","first-page":"2429","DOI":"10.2174\/092986707782023695","volume":"14","author":"W Fischer","year":"2007","unstructured":"Fischer W, Krugel U (2007) P2Y receptors: focus on structural, pharmacological and functional aspects in the brain. Curr Med Chem 14:2429\u20132455","journal-title":"Curr Med Chem"},{"key":"4461_CR28","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/S0306-4522(03)00228-8","volume":"120","author":"F Cavaliere","year":"2003","unstructured":"Cavaliere F, Florenzano F, Amadio S, Fusco FR, Viscomi MT, D\u2019Ambrosi N, Vacca F, Sancesario G, Bernardi G, Molinari M, Volonte C (2003) Up-regulation of P2X2, P2X4 receptor and ischemic cell death: prevention by P2 antagonists. Neuroscience 120:85\u201398","journal-title":"Neuroscience"},{"key":"4461_CR29","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.pharmthera.2005.06.002","volume":"109","author":"H Franke","year":"2006","unstructured":"Franke H, Illes P (2006) Involvement of P2 receptors in the growth and survival of neurons in the CNS. Pharmacol Ther 109:297\u2013324","journal-title":"Pharmacol Ther"},{"key":"4461_CR30","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1002\/cne.21527","volume":"506","author":"A Casanovas","year":"2008","unstructured":"Casanovas A, Hernandez S, Tarabal O, Rossello J, Esquerda JE (2008) Strong P2X4 purinergic receptor-like immunoreactivity is selectively associated with degenerating neurons in transgenic rodent models of amyotrophic lateral sclerosis. J Comp Neurol 506:75\u201392","journal-title":"J Comp Neurol"},{"key":"4461_CR31","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1111\/j.1742-4658.2008.06796.x","volume":"276","author":"S Apolloni","year":"2009","unstructured":"Apolloni S, Montilli C, Finocchi P, Amadio S (2009) Membrane compartments and purinergic signalling: P2X receptors in neurodegenerative and neuroinflammatory events. Febs J 276:354\u2013364","journal-title":"Febs J"},{"key":"4461_CR32","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201708743","volume":"10","author":"A Zabala","year":"2018","unstructured":"Zabala A, Vazquez-Villoldo N, Rissiek B, Gejo J, Martin A, Palomino A, Perez-Samartin A, Pulagam KR, Lukowiak M, Capetillo-Zarate E et al (2018) P2X4 receptor controls microglia activation and favors remyelination in autoimmune encephalitis. EMBO Mol Med 10:e8743","journal-title":"EMBO Mol Med"},{"key":"4461_CR33","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2021.102139","volume":"206","author":"K Carvalho","year":"2021","unstructured":"Carvalho K, Martin E, Ces A, Sarrazin N, Lagouge-Roussey P, Nous C, Boucherit L, Youssef I, Prigent A, Faivre E et al (2021) P2X7-deficiency improves plasticity and cognitive abilities in a mouse model of Tauopathy. Prog Neurobiol 206:102139","journal-title":"Prog Neurobiol"},{"issue":"14","key":"4461_CR34","doi-asserted-by":"publisher","first-page":"2290","DOI":"10.1038\/emboj.2010.126","volume":"29","author":"L Ulmann","year":"2010","unstructured":"Ulmann L, Hirbec H, Rassendren F (2010) P2X4 receptors mediate PGE2 release by tissue-resident macrophages and initiate inflammatory pain. EMBO J 29(14):2290\u2013300","journal-title":"EMBO J"},{"key":"4461_CR35","doi-asserted-by":"publisher","first-page":"9454275","DOI":"10.1155\/2017\/9454275","volume":"2017","author":"E Bou\u00e9-Grabot","year":"2017","unstructured":"Bou\u00e9-Grabot E, Pankratov Y (2017) Modulation of central synapses by astrocyte-released ATP and postsynaptic P2X receptors. Neural Plast 2017:9454275","journal-title":"Neural Plast"},{"key":"4461_CR36","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.tins.2008.10.001","volume":"32","author":"MP Abbracchio","year":"2009","unstructured":"Abbracchio MP, Burnstock G, Verkhratsky A, Zimmermann H (2009) Purinergic signalling in the nervous system: an overview. Trends Neurosci 32:19\u201329","journal-title":"Trends Neurosci"},{"key":"4461_CR37","doi-asserted-by":"publisher","first-page":"5562","DOI":"10.3390\/ijms21155562","volume":"21","author":"A Montilla","year":"2020","unstructured":"Montilla A, Mata GP, Matute C, Domercq M (2020) Contribution of P2X4 receptors to CNS function and pathophysiology. Int J Mol Sci 21:5562","journal-title":"Int J Mol Sci"},{"key":"4461_CR38","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1007\/s12264-020-00570-y","volume":"36","author":"A Duveau","year":"2020","unstructured":"Duveau A, Bertin E, Boue-Grabot E (2020) Implication of Neuronal Versus Microglial P2X4 Receptors in Central Nervous System Disorders. Neurosci Bull 36:1327\u20131343","journal-title":"Neurosci Bull"},{"key":"4461_CR39","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1083\/jcb.201409071","volume":"209","author":"Q Cao","year":"2015","unstructured":"Cao Q, Zhong XZ, Zou Y, Murrell-Lagnado R, Zhu MX, Dong XP (2015) Calcium release through P2X4 activates calmodulin to promote endolysosomal membrane fusion. J Cell Biol 209:879\u2013894","journal-title":"J Cell Biol"},{"key":"4461_CR40","doi-asserted-by":"publisher","first-page":"17658","DOI":"10.1074\/jbc.M114.552158","volume":"289","author":"P Huang","year":"2014","unstructured":"Huang P, Zou Y, Zhong XZ, Cao Q, Zhao K, Zhu MX, Murrell-Lagnado R, Dong XP (2014) P2X4 forms functional ATP-activated cation channels on lysosomal membranes regulated by luminal pH. J Biol Chem 289:17658\u201317667","journal-title":"J Biol Chem"},{"key":"4461_CR41","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1085\/jgp.200910336","volume":"135","author":"E Toulme","year":"2010","unstructured":"Toulme E, Garcia A, Samways D, Egan TM, Carson MJ, Khakh BS (2010) P2X4 receptors in activated C8\u2013B4 cells of cerebellar microglial origin. J Gen Physiol 135:333\u2013353","journal-title":"J Gen Physiol"},{"key":"4461_CR42","doi-asserted-by":"publisher","first-page":"233","DOI":"10.3389\/fncel.2013.00233","volume":"7","author":"LE Robinson","year":"2013","unstructured":"Robinson LE, Murrell-Lagnado RD (2013) The trafficking and targeting of P2X receptors. Front Cell Neurosci 7:233","journal-title":"Front Cell Neurosci"},{"key":"4461_CR43","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1038\/nn.3155","volume":"15","author":"S Beggs","year":"2012","unstructured":"Beggs S, Trang T, Salter MW (2012) P2X4R+ microglia drive neuropathic pain. Nat Neurosci 15:1068\u20131073","journal-title":"Nat Neurosci"},{"key":"4461_CR44","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s12017-009-8073-2","volume":"11","author":"R Varma","year":"2009","unstructured":"Varma R, Chai Y, Troncoso J, Gu J, Xing H, Stojilkovic SS, Mattson MP, Haughey NJ (2009) Amyloid-beta induces a caspase-mediated cleavage of P2X4 to promote purinotoxicity. Neuromol Med 11:63\u201375","journal-title":"Neuromol Med"},{"key":"4461_CR45","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.nbd.2006.08.018","volume":"25","author":"M Andries","year":"2007","unstructured":"Andries M, Van Damme P, Robberecht W, Van Den Bosch L (2007) Ivermectin inhibits AMPA receptor-mediated excitotoxicity in cultured motor neurons and extends the life span of a transgenic mouse model of amyotrophic lateral sclerosis. Neurobiol Dis 25:8\u201316","journal-title":"Neurobiol Dis"},{"key":"4461_CR46","doi-asserted-by":"publisher","first-page":"4648","DOI":"10.4049\/jimmunol.0901212","volume":"183","author":"N D'Ambrosi","year":"2009","unstructured":"D\u2019Ambrosi N, Finocchi P, Apolloni S, Cozzolino M, Ferri A, Padovano V, Pietrini G, Carri MT, Volonte C (2009) The proinflammatory action of microglial P2 receptors is enhanced in SOD1 models for amyotrophic lateral sclerosis. J Immunol 183:4648\u20134656","journal-title":"J Immunol"},{"key":"4461_CR47","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1038\/nature01786","volume":"424","author":"M Tsuda","year":"2003","unstructured":"Tsuda M, Shigemoto-Mogami Y, Koizumi S, Mizokoshi A, Kohsaka S, Salter MW, Inoue K (2003) P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature 424:778\u2013783","journal-title":"Nature"},{"key":"4461_CR48","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1038\/s41380-019-0641-8","volume":"26","author":"E Bertin","year":"2021","unstructured":"Bertin E, Deluc T, Pilch KS, Martinez A, Pougnet JT, Doudnikoff E, Allain AE, Bergmann P, Russeau M, Toulme E et al (2021) Increased surface P2X4 receptor regulates anxiety and memory in P2X4 internalization-defective knock-in mice. Mol Psychiatry 26:629\u2013644","journal-title":"Mol Psychiatry"},{"key":"4461_CR49","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1097\/NEN.0b013e3181cd3e33","volume":"69","author":"S Hernandez","year":"2010","unstructured":"Hernandez S, Casanovas A, Piedrafita L, Tarabal O, Esquerda JE (2010) Neurotoxic species of misfolded SOD1G93A recognized by antibodies against the P2X4 subunit of the ATP receptor accumulate in damaged neurons of transgenic animal models of amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 69:176\u2013187","journal-title":"J Neuropathol Exp Neurol"},{"key":"4461_CR50","doi-asserted-by":"publisher","first-page":"9006","DOI":"10.1523\/JNEUROSCI.2370-06.2006","volume":"26","author":"JA Sim","year":"2006","unstructured":"Sim JA, Chaumont S, Jo J, Ulmann L, Young MT, Cho K, Buell G, North RA, Rassendren F (2006) Altered hippocampal synaptic potentiation in P2X4 knock-out mice. J Neurosci 26:9006\u20139009","journal-title":"J Neurosci"},{"key":"4461_CR51","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1016\/S0306-4522(02)00205-1","volume":"114","author":"PO Fernagut","year":"2002","unstructured":"Fernagut PO, Diguet E, Stefanova N, Biran M, Wenning GK, Canioni P, Bioulac B, Tison F (2002) Subacute systemic 3-nitropropionic acid intoxication induces a distinct motor disorder in adult C57Bl\/6 mice: behavioural and histopathological characterisation. Neuroscience 114:1005\u20131017","journal-title":"Neuroscience"},{"key":"4461_CR52","doi-asserted-by":"publisher","first-page":"19993","DOI":"10.1074\/jbc.M111.231324","volume":"286","author":"YH Jo","year":"2011","unstructured":"Jo YH, Donier E, Martinez A, Garret M, Toulme E, Boue-Grabot E (2011) Cross-talk between P2X4 and gamma-aminobutyric acid, type A receptors determines synaptic efficacy at a central synapse. J Biol Chem 286:19993\u201320004","journal-title":"J Biol Chem"},{"key":"4461_CR53","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1124\/mol.105.018812","volume":"69","author":"E Toulme","year":"2006","unstructured":"Toulme E, Soto F, Garret M, Boue-Grabot E (2006) Functional properties of internalization-deficient P2X4 receptors reveal a novel mechanism of ligand-gated channel facilitation by ivermectin. Mol Pharmacol 69:576\u2013587","journal-title":"Mol Pharmacol"},{"key":"4461_CR54","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1007\/978-1-4939-9717-6_18","volume":"2041","author":"E Bertin","year":"2020","unstructured":"Bertin E, Martinez A, Boue-Grabot E (2020) P2X electrophysiology and surface trafficking in Xenopus oocytes. Methods Mol Biol 2041:243\u2013259","journal-title":"Methods Mol Biol"},{"key":"4461_CR55","first-page":"1488","volume":"35","author":"A Ray","year":"2010","unstructured":"Ray A, Dittel BN (2010) Isolation of mouse peritoneal cavity cells. J Vis Exp 35:1488","journal-title":"J Vis Exp"},{"key":"4461_CR56","doi-asserted-by":"publisher","first-page":"4814","DOI":"10.1523\/JNEUROSCI.22-12-04814.2002","volume":"22","author":"LK Bobanovic","year":"2002","unstructured":"Bobanovic LK, Royle SJ, Murrell-Lagnado RD (2002) P2X receptor trafficking in neurons is subunit specific. J Neurosci 22:4814\u20134824","journal-title":"J Neurosci"},{"key":"4461_CR57","doi-asserted-by":"publisher","first-page":"35378","DOI":"10.1074\/jbc.M204844200","volume":"277","author":"SJ Royle","year":"2002","unstructured":"Royle SJ, Bobanovic LK, Murrell-Lagnado RD (2002) Identification of a non-canonical tyrosine-based endocytic motif in an ionotropic receptor. J Biol Chem 277:35378\u201335385","journal-title":"J Biol Chem"},{"key":"4461_CR58","doi-asserted-by":"publisher","first-page":"3073","DOI":"10.1242\/jcs.02451","volume":"118","author":"SJ Royle","year":"2005","unstructured":"Royle SJ, Qureshi OS, Bobanovic LK, Evans PR, Owen DJ, Murrell-Lagnado RD (2005) Non-canonical YXXGPhi endocytic motifs: recognition by AP2 and preferential utilization in P2X4 receptors. J Cell Sci 118:3073\u20133080","journal-title":"J Cell Sci"},{"key":"4461_CR59","first-page":"733","volume":"18","author":"M Adencreutz","year":"2004","unstructured":"Adencreutz M, Hau J (2004) Studies of neonatal and juvenile neuromuscular locomotor development of C57BL\/6\/Bkl, 129SvEv\/Bkl and F1 hybrid mice in swim tests. In Vivo 18:733\u2013737","journal-title":"In Vivo"},{"key":"4461_CR60","doi-asserted-by":"publisher","first-page":"498","DOI":"10.3389\/fncel.2019.00498","volume":"13","author":"P Bergmann","year":"2019","unstructured":"Bergmann P, Garcia de Paco E, Rissiek B, Menzel S, Dubberke G, Hua J, Rassendren F, Ulmann L, Koch-Nolte F (2019) Generation and characterization of specific monoclonal antibodies and nanobodies directed against the ATP-gated channel P2X4. Front Cell Neurosci 13:498","journal-title":"Front Cell Neurosci"},{"key":"4461_CR61","doi-asserted-by":"publisher","first-page":"8902","DOI":"10.1523\/JNEUROSCI.1496-16.2016","volume":"36","author":"J Xu","year":"2016","unstructured":"Xu J, Bernstein AM, Wong A, Lu XH, Khoja S, Yang XW, Davies DL, Micevych P, Sofroniew MV, Khakh BS (2016) P2X4 receptor reporter mice: sparse brain expression and feeding-related presynaptic facilitation in the arcuate nucleus. J Neurosci 36:8902\u20138920","journal-title":"J Neurosci"},{"key":"4461_CR62","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1556\/APhysiol.98.2011.1.4","volume":"98","author":"D Bataveljic","year":"2011","unstructured":"Bataveljic D, Stamenkovic S, Bacic G, Andjus PR (2011) Imaging cellular markers of neuroinflammation in the brain of the rat model of amyotrophic lateral sclerosis. Acta Physiol Hung 98:27\u201331","journal-title":"Acta Physiol Hung"},{"key":"4461_CR63","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052941","volume":"7","author":"P Corcia","year":"2012","unstructured":"Corcia P, Tauber C, Vercoullie J, Arlicot N, Prunier C, Praline J, Nicolas G, Venel Y, Hommet C, Baulieu JL et al (2012) Molecular imaging of microglial activation in amyotrophic lateral sclerosis. PLoS ONE 7:e52941","journal-title":"PLoS ONE"},{"key":"4461_CR64","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/1742-2094-11-55","volume":"11","author":"KE Lewis","year":"2014","unstructured":"Lewis KE, Rasmussen AL, Bennett W, King A, West AK, Chung RS, Chuah MI (2014) Microglia and motor neurons during disease progression in the SOD1G93A mouse model of amyotrophic lateral sclerosis: changes in arginase1 and inducible nitric oxide synthase. J Neuroinflammation 11:55","journal-title":"J Neuroinflammation"},{"key":"4461_CR65","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.3389\/fimmu.2017.01005","volume":"8","author":"J Liu","year":"2017","unstructured":"Liu J, Wang F (2017) Role of neuroinflammation in amyotrophic lateral sclerosis: cellular mechanisms and therapeutic implications. Front Immunol 8:1005","journal-title":"Front Immunol"},{"key":"4461_CR66","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/S1474-4422(11)70015-1","volume":"10","author":"T Philips","year":"2011","unstructured":"Philips T, Robberecht W (2011) Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease. Lancet Neurol 10:253\u2013263","journal-title":"Lancet Neurol"},{"issue":"12","key":"4461_CR67","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1136\/jnnp-2019-ABN-2.3","volume":"90","author":"AG Thompson","year":"2019","unstructured":"Thompson AG, Turner MR (2019) Untangling neuroinflammation in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 90(12):1303\u20131304","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"4461_CR68","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.nbd.2003.12.012","volume":"15","author":"MR Turner","year":"2004","unstructured":"Turner MR, Cagnin A, Turkheimer FE, Miller CC, Shaw CE, Brooks DJ, Leigh PN, Banati RB (2004) Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study. Neurobiol Dis 15:601\u2013609","journal-title":"Neurobiol Dis"},{"key":"4461_CR69","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1097\/00001756-200504250-00001","volume":"16","author":"P Weydt","year":"2005","unstructured":"Weydt P, Moller T (2005) Neuroinflammation in the pathogenesis of amyotrophic lateral sclerosis. NeuroReport 16:527\u2013531","journal-title":"NeuroReport"},{"key":"4461_CR70","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.nicl.2015.01.009","volume":"7","author":"NR Zurcher","year":"2015","unstructured":"Zurcher NR, Loggia ML, Lawson R, Chonde DB, Izquierdo-Garcia D, Yasek JE, Akeju O, Catana C, Rosen BR, Cudkowicz ME et al (2015) Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: assessed with [(11)C]-PBR28. Neuroimage Clin 7:409\u2013414","journal-title":"Neuroimage Clin"},{"key":"4461_CR71","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/j.nurt.2010.05.012","volume":"7","author":"MR Vargas","year":"2010","unstructured":"Vargas MR, Johnson JA (2010) Astrogliosis in amyotrophic lateral sclerosis: role and therapeutic potential of astrocytes. Neurotherapeutics 7:471\u2013481","journal-title":"Neurotherapeutics"},{"key":"4461_CR72","doi-asserted-by":"publisher","first-page":"2261","DOI":"10.3390\/ijms18112261","volume":"18","author":"JA Layhadi","year":"2017","unstructured":"Layhadi JA, Fountain SJ (2017) P2X4 receptor-dependent Ca(2+) influx in model human monocytes and macrophages. Int J Mol Sci 18:2261","journal-title":"Int J Mol Sci"},{"key":"4461_CR73","first-page":"537","volume":"77","author":"O Komine","year":"2015","unstructured":"Komine O, Yamanaka K (2015) Neuroinflammation in motor neuron disease. Nagoya J Med Sci 77:537\u2013549","journal-title":"Nagoya J Med Sci"},{"key":"4461_CR74","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1212\/WNL.57.7.1282","volume":"57","author":"ME Alexianu","year":"2001","unstructured":"Alexianu ME, Kozovska M, Appel SH (2001) Immune reactivity in a mouse model of familial ALS correlates with disease progression. Neurology 57:1282\u20131289","journal-title":"Neurology"},{"key":"4461_CR75","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1002\/(SICI)1098-1136(199807)23:3<249::AID-GLIA7>3.0.CO;2-#","volume":"23","author":"ED Hall","year":"1998","unstructured":"Hall ED, Oostveen JA, Gurney ME (1998) Relationship of microglial and astrocytic activation to disease onset and progression in a transgenic model of familial ALS. Glia 23:249\u2013256","journal-title":"Glia"},{"key":"4461_CR76","doi-asserted-by":"publisher","first-page":"3771","DOI":"10.1038\/ncomms4771","volume":"5","author":"T Masuda","year":"2014","unstructured":"Masuda T, Iwamoto S, Yoshinaga R, Tozaki-Saitoh H, Nishiyama A, Mak TW, Tamura T, Tsuda M, Inoue K (2014) Transcription factor IRF5 drives P2X4R+-reactive microglia gating neuropathic pain. Nat Commun 5:3771","journal-title":"Nat Commun"},{"key":"4461_CR77","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.neuron.2007.03.020","volume":"54","author":"SD Silberberg","year":"2007","unstructured":"Silberberg SD, Li M, Swartz KJ (2007) Ivermectin Interaction with transmembrane helices reveals widespread rearrangements during opening of P2X receptor channels. Neuron 54:263\u2013274","journal-title":"Neuron"},{"key":"4461_CR78","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1007\/s11302-012-9336-1","volume":"9","author":"L Stokes","year":"2012","unstructured":"Stokes L (2012) Rab5 regulates internalisation of P2X4 receptors and potentiation by ivermectin. Purinergic Signal 9:113\u2013121","journal-title":"Purinergic Signal"},{"key":"4461_CR79","doi-asserted-by":"publisher","first-page":"148","DOI":"10.3389\/fnins.2015.00148","volume":"9","author":"RJ Rodrigues","year":"2015","unstructured":"Rodrigues RJ, Tome AR, Cunha RA (2015) ATP as a multi-target danger signal in the brain. Front Neurosci 9:148","journal-title":"Front Neurosci"},{"key":"4461_CR80","doi-asserted-by":"publisher","first-page":"4102","DOI":"10.1093\/hmg\/ddt259","volume":"22","author":"S Apolloni","year":"2013","unstructured":"Apolloni S, Amadio S, Montilli C, Volonte C, D\u2019Ambrosi N (2013) Ablation of P2X7 receptor exacerbates gliosis and motoneuron death in the SOD1-G93A mouse model of amyotrophic lateral sclerosis. Hum Mol Genet 22:4102\u20134116","journal-title":"Hum Mol Genet"},{"key":"4461_CR81","first-page":"1101","volume":"7","author":"S Apolloni","year":"2014","unstructured":"Apolloni S, Amadio S, Parisi C, Matteucci A, Potenza RL, Armida M, Popoli P, D\u2019Ambrosi N, Volonte C (2014) Spinal cord pathology is ameliorated by P2X7 antagonism in a SOD1-mutant mouse model of amyotrophic lateral sclerosis. Dis Model Mech 7:1101\u20131109","journal-title":"Dis Model Mech"},{"key":"4461_CR82","doi-asserted-by":"publisher","first-page":"2920","DOI":"10.1038\/s41388-022-02297-8","volume":"41","author":"S Chadet","year":"2022","unstructured":"Chadet S, Allard J, Brisson L, Lopez-Charcas O, Lemoine R, Heraud A, Lerondel S, Guibon R, Fromont G, Le Pape A et al (2022) P2x4 receptor promotes mammary cancer progression by sustaining autophagy and associated mesenchymal transition. Oncogene 41:2920\u20132931","journal-title":"Oncogene"},{"key":"4461_CR83","doi-asserted-by":"publisher","first-page":"11263","DOI":"10.1523\/JNEUROSCI.2308-08.2008","volume":"28","author":"L Ulmann","year":"2008","unstructured":"Ulmann L, Hatcher JP, Hughes JP, Chaumont S, Green PJ, Conquet F, Buell GN, Reeve AJ, Chessell IP, Rassendren F (2008) Up-regulation of P2X4 receptors in spinal microglia after peripheral nerve injury mediates BDNF release and neuropathic pain. J Neurosci 28:11263\u201311268","journal-title":"J Neurosci"},{"key":"4461_CR84","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.3390\/ijms22041636","volume":"22","author":"A Gomez Morillas","year":"2021","unstructured":"Gomez Morillas A, Besson VC, Lerouet D (2021) Microglia and neuroinflammation: what place for P2RY12? Int J Mol Sci 22:1636","journal-title":"Int J Mol Sci"},{"key":"4461_CR85","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.4049\/jimmunol.1700965","volume":"200","author":"JA Layhadi","year":"2018","unstructured":"Layhadi JA, Turner J, Crossman D, Fountain SJ (2018) ATP evokes Ca(2+) responses and CXCL5 secretion via P2X4 receptor activation in human monocyte-derived macrophages. J Immunol 200:1159\u20131168","journal-title":"J Immunol"},{"key":"4461_CR86","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.99431","volume":"3","author":"B Csoka","year":"2018","unstructured":"Csoka B, Nemeth ZH, Szabo I, Davies DL, Varga ZV, Paloczi J, Falzoni S, Di Virgilio F, Muramatsu R, Yamashita T et al (2018) Macrophage P2X4 receptors augment bacterial killing and protect against sepsis. JCI Insight 3:e99431","journal-title":"JCI Insight"},{"key":"4461_CR87","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.bj.2017.06.010","volume":"40","author":"J Suurvali","year":"2017","unstructured":"Suurvali J, Boudinot P, Kanellopoulos J, Ruutel Boudinot S (2017) P2X4: A fast and sensitive purinergic receptor. Biomed J 40:245\u2013256","journal-title":"Biomed J"},{"key":"4461_CR88","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.expneurol.2016.01.008","volume":"277","author":"JM Van Dyke","year":"2016","unstructured":"Van Dyke JM, Smit-Oistad IM, Macrander C, Krakora D, Meyer MG, Suzuki M (2016) Macrophage-mediated inflammation and glial response in the skeletal muscle of a rat model of familial amyotrophic lateral sclerosis (ALS). Exp Neurol 277:275\u2013282","journal-title":"Exp Neurol"},{"key":"4461_CR89","doi-asserted-by":"publisher","first-page":"831","DOI":"10.3390\/ijms19030831","volume":"19","author":"S Mammana","year":"2018","unstructured":"Mammana S, Fagone P, Cavalli E, Basile MS, Petralia MC, Nicoletti F, Bramanti P, Mazzon E (2018) The role of macrophages in neuroinflammatory and neurodegenerative pathways of Alzheimer\u2019s disease, amyotrophic lateral sclerosis, and multiple sclerosis: pathogenetic cellular effectors and potential therapeutic targets. Int J Mol Sci 19:831","journal-title":"Int J Mol Sci"},{"key":"4461_CR90","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/1742-2094-7-8","volume":"7","author":"DJ Graber","year":"2010","unstructured":"Graber DJ, Hickey WF, Harris BT (2010) Progressive changes in microglia and macrophages in spinal cord and peripheral nerve in the transgenic rat model of amyotrophic lateral sclerosis. J Neuroinflammation 7:8","journal-title":"J Neuroinflammation"},{"key":"4461_CR91","first-page":"60","volume":"1","author":"G Liu","year":"2012","unstructured":"Liu G, Fiala M, Mizwicki MT, Sayre J, Magpantay L, Siani A, Mahanian M, Chattopadhyay M, La Cava A, Wiedau-Pazos M (2012) Neuronal phagocytosis by inflammatory macrophages in ALS spinal cord: inhibition of inflammation by resolvin D1. Am J Neurodegener Dis 1:60\u201374","journal-title":"Am J Neurodegener Dis"},{"key":"4461_CR92","doi-asserted-by":"publisher","first-page":"3838","DOI":"10.1242\/jcs.010348","volume":"120","author":"OS Qureshi","year":"2007","unstructured":"Qureshi OS, Paramasivam A, Yu JC, Murrell-Lagnado RD (2007) Regulation of P2X4 receptors by lysosomal targeting, glycan protection and exocytosis. J Cell Sci 120:3838\u20133849","journal-title":"J Cell Sci"},{"key":"4461_CR93","doi-asserted-by":"publisher","first-page":"3063","DOI":"10.1172\/JCI62636","volume":"122","author":"O Butovsky","year":"2012","unstructured":"Butovsky O, Siddiqui S, Gabriely G, Lanser AJ, Dake B, Murugaiyan G, Doykan CE, Wu PM, Gali RR, Iyer LK et al (2012) Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS. J Clin Invest 122:3063\u20133087","journal-title":"J Clin Invest"},{"key":"4461_CR94","doi-asserted-by":"crossref","unstructured":"Zondler L, Muller K, Khalaji S, Bliederhauser C, Ruf WP, Grozdanov V, Thiemann M, Fundel-Clemes K, Freischmidt A, Holzmann K, et al (2016) Peripheral monocytes are functionally altered and invade the CNS in ALS patients. Acta Neuropathol 132: 391\u2013411.","DOI":"10.1007\/s00401-016-1548-y"}],"container-title":["Cellular and Molecular Life Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00018-022-04461-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00018-022-04461-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00018-022-04461-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T18:50:08Z","timestamp":1700851808000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00018-022-04461-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,19]]},"references-count":94,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["4461"],"URL":"https:\/\/doi.org\/10.1007\/s00018-022-04461-5","relation":{},"ISSN":["1420-682X","1420-9071"],"issn-type":[{"value":"1420-682X","type":"print"},{"value":"1420-9071","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,19]]},"assertion":[{"value":"29 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 May 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 July 2022","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":"Conflict of interest"}},{"value":"All experimental procedures complied with official European guidelines for the care and use of laboratory animals (Directive 2010\/63\/UE) and were approved by the ethical committee of Bordeaux (CEEA-50).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"431"}}