{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:18:10Z","timestamp":1792160290632,"version":"4.4.0"},"reference-count":42,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2020,3,1]],"date-time":"2020-03-01T00:00:00Z","timestamp":1583020800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,3,1]],"date-time":"2020-03-01T00:00:00Z","timestamp":1583020800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2019,12,18]],"date-time":"2019-12-18T00:00:00Z","timestamp":1576627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013278","name":"EU Joint Programme \u2013 Neurodegenerative Disease Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013278","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neuron"],"published-print":{"date-parts":[[2020,3]]},"DOI":"10.1016\/j.neuron.2019.12.014","type":"journal-article","created":{"date-parts":[[2020,1,7]],"date-time":"2020-01-07T10:43:36Z","timestamp":1578393816000},"page":"855-866.e5","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":217,"title":["Astrocyte Unfolded Protein Response Induces a Specific Reactivity State that Causes Non-Cell-Autonomous Neuronal Degeneration"],"prefix":"10.1016","volume":"105","author":[{"given":"Heather L.","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver J.","family":"Freeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian J.","family":"Butcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Staffan","family":"Holmqvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Humoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Sch\u00e4tzl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel T.","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas C.","family":"Verity","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean P.","family":"Swinden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Hayes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lis","family":"de Weerd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Rowitch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin J.M.","family":"Franklin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna R.","family":"Mallucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.neuron.2019.12.014_bib1","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/nature11059","article-title":"Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors","volume":"486","author":"Allen","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.neuron.2019.12.014_bib2","doi-asserted-by":"crossref","first-page":"7193","DOI":"10.1021\/jm300713s","article-title":"Discovery of 7-methyl-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (GSK2606414), a potent and selective first-in-class inhibitor of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)","volume":"55","author":"Axten","year":"2012","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.neuron.2019.12.014_bib3","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.cub.2017.01.047","article-title":"RTN3 is a novel cold-induced protein and mediates neuroprotective effects of RBM3","volume":"27","author":"Bastide","year":"2017","journal-title":"Curr. Biol."},{"key":"10.1016\/j.neuron.2019.12.014_bib4","doi-asserted-by":"crossref","first-page":"e2271","DOI":"10.1038\/cddis.2016.173","article-title":"Mitofusin-mediated ER stress triggers neurodegeneration in pink1\/parkin models of Parkinson\u2019s disease","volume":"7","author":"Celardo","year":"2016","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.neuron.2019.12.014_bib5","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.cell.2004.12.020","article-title":"Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis","volume":"120","author":"Christopherson","year":"2005","journal-title":"Cell"},{"key":"10.1016\/j.neuron.2019.12.014_bib6","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/nature12776","article-title":"Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways","volume":"504","author":"Chung","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.neuron.2019.12.014_bib7","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.cell.2007.01.050","article-title":"eIF2alpha phosphorylation bidirectionally regulates the switch from short- to long-term synaptic plasticity and memory","volume":"129","author":"Costa-Mattioli","year":"2007","journal-title":"Cell"},{"key":"10.1016\/j.neuron.2019.12.014_bib8","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1097\/00001756-200107030-00052","article-title":"Burrowing into prion disease","volume":"12","author":"Deacon","year":"2001","journal-title":"Neuroreport"},{"key":"10.1016\/j.neuron.2019.12.014_bib9","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3389\/fnana.2018.00040","article-title":"Shaping synapses by the neural extracellular matrix","volume":"12","author":"Ferrer-Ferrer","year":"2018","journal-title":"Front. Neuroanat."},{"key":"10.1016\/j.neuron.2019.12.014_bib10","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1093\/hmg\/ddy152","article-title":"PERK inhibition delays neurodegeneration and improves motor function in a mouse model of Marinesco-Sj\u00f6gren syndrome","volume":"27","author":"Grande","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.neuron.2019.12.014_bib11","doi-asserted-by":"crossref","first-page":"15830","DOI":"10.1074\/jbc.M116.738021","article-title":"Attenuation of PKR-like ER kinase (PERK) signaling selectively controls endoplasmic reticulum stress-induced inflammation without compromising immunological responses","volume":"291","author":"Guthrie","year":"2016","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2019.12.014_bib12","doi-asserted-by":"crossref","first-page":"e1672","DOI":"10.1038\/cddis.2015.49","article-title":"Partial restoration of protein synthesis rates by the small molecule ISRIB prevents neurodegeneration without pancreatic toxicity","volume":"6","author":"Halliday","year":"2015","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.neuron.2019.12.014_bib13","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1093\/brain\/awx074","article-title":"Repurposed drugs targeting eIF2&\u03b1;-P-mediated translational repression prevent neurodegeneration in mice","volume":"140","author":"Halliday","year":"2017","journal-title":"Brain"},{"key":"10.1016\/j.neuron.2019.12.014_bib14","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s40478-019-0735-1","article-title":"Complement 3+-astrocytes are highly abundant in prion diseases, but their abolishment led to an accelerated disease course and early dysregulation of microglia","volume":"7","author":"Hartmann","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"10.1016\/j.neuron.2019.12.014_bib15","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.pneurobio.2018.02.002","article-title":"Cell adhesion and matricellular support by astrocytes of the tripartite synapse","volume":"165-167","author":"Hillen","year":"2018","journal-title":"Prog. Neurobiol."},{"key":"10.1016\/j.neuron.2019.12.014_bib16","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s00401-005-1038-0","article-title":"The unfolded protein response is activated in Alzheimer\u2019s disease","volume":"110","author":"Hoozemans","year":"2005","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.neuron.2019.12.014_bib17","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.bbrc.2007.01.043","article-title":"Activation of the unfolded protein response in Parkinson\u2019s disease","volume":"354","author":"Hoozemans","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.neuron.2019.12.014_bib18","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.2353\/ajpath.2009.080814","article-title":"The unfolded protein response is activated in pretangle neurons in Alzheimer\u2019s disease hippocampus","volume":"174","author":"Hoozemans","year":"2009","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.neuron.2019.12.014_bib19","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/ng.2853","article-title":"Therapeutic modulation of eIF2\u03b1 phosphorylation rescues TDP-43 toxicity in amyotrophic lateral sclerosis disease models","volume":"46","author":"Kim","year":"2014","journal-title":"Nat. Genet."},{"key":"10.1016\/j.neuron.2019.12.014_bib20","doi-asserted-by":"crossref","first-page":"E440","DOI":"10.1073\/pnas.1104977108","article-title":"Control of excitatory CNS synaptogenesis by astrocyte-secreted proteins Hevin and SPARC","volume":"108","author":"Kucukdereli","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2019.12.014_bib21","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"10.1016\/j.neuron.2019.12.014_bib22","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1038\/nn.3486","article-title":"Suppression of eIF2\u03b1 kinases alleviates Alzheimer\u2019s disease-related plasticity and memory deficits","volume":"16","author":"Ma","year":"2013","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.neuron.2019.12.014_bib23","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/s41419-019-1523-3","article-title":"The unfolded protein response modulators GSK2606414 and KIRA6 are potent KIT inhibitors","volume":"10","author":"Mahameed","year":"2019","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.neuron.2019.12.014_bib24","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1093\/emboj\/21.3.202","article-title":"Post-natal knockout of prion protein alters hippocampal CA1 properties, but does not result in neurodegeneration","volume":"21","author":"Mallucci","year":"2002","journal-title":"EMBO J."},{"key":"10.1016\/j.neuron.2019.12.014_bib25","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1126\/science.1090187","article-title":"Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis","volume":"302","author":"Mallucci","year":"2003","journal-title":"Science"},{"key":"10.1016\/j.neuron.2019.12.014_bib26","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.neuron.2007.01.005","article-title":"Targeting cellular prion protein reverses early cognitive deficits and neurophysiological dysfunction in prion-infected mice","volume":"53","author":"Mallucci","year":"2007","journal-title":"Neuron"},{"key":"10.1016\/j.neuron.2019.12.014_bib27","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.nbd.2018.01.004","article-title":"Targeting PERK signaling with the small molecule GSK2606414 prevents neurodegeneration in a model of Parkinson\u2019s disease","volume":"112","author":"Mercado","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.neuron.2019.12.014_bib28","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nature11058","article-title":"Sustained translational repression by eIF2\u03b1-P mediates prion neurodegeneration","volume":"485","author":"Moreno","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.neuron.2019.12.014_bib29","doi-asserted-by":"crossref","first-page":"206ra138","DOI":"10.1126\/scitranslmed.3006767","article-title":"Oral treatment targeting the unfolded protein response prevents neurodegeneration and clinical disease in prion-infected mice","volume":"5","author":"Moreno","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.neuron.2019.12.014_bib30","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1002\/path.3969","article-title":"The unfolded protein response is associated with early tau pathology in the hippocampus of tauopathies","volume":"226","author":"Nijholt","year":"2012","journal-title":"J.\u00a0Pathol."},{"key":"10.1016\/j.neuron.2019.12.014_bib31","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/nature14142","article-title":"RBM3 mediates structural plasticity and protective effects of cooling in neurodegeneration","volume":"518","author":"Peretti","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.neuron.2019.12.014_bib32","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s00401-015-1487-z","article-title":"PERK inhibition prevents tau-mediated neurodegeneration in a mouse model of frontotemporal dementia","volume":"130","author":"Radford","year":"2015","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.neuron.2019.12.014_bib33","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1038\/cdd.2017.58","article-title":"When PERK inhibitors turn out to be new potent RIPK1 inhibitors: critical issues on the specificity and use of GSK2606414 and GSK2656157","volume":"24","author":"Rojas-Rivera","year":"2017","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.neuron.2019.12.014_bib34","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nrm2199","article-title":"Signal integration in the endoplasmic reticulum unfolded protein response","volume":"8","author":"Ron","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.neuron.2019.12.014_bib35","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1002\/ana.410350314","article-title":"Childhood ataxia with diffuse central nervous system hypomyelination","volume":"35","author":"Schiffmann","year":"1994","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.neuron.2019.12.014_bib36","doi-asserted-by":"crossref","first-page":"e00498","DOI":"10.7554\/eLife.00498","article-title":"Pharmacological brake-release of mRNA translation enhances cognitive memory","volume":"2","author":"Sidrauski","year":"2013","journal-title":"eLife"},{"key":"10.1016\/j.neuron.2019.12.014_bib37","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1093\/brain\/aww101","article-title":"The unfolded protein response: mechanisms and therapy of neurodegeneration","volume":"139","author":"Smith","year":"2016","journal-title":"Brain"},{"key":"10.1016\/j.neuron.2019.12.014_bib38","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1111\/jnc.14642","article-title":"Endoplasmic reticulum stress is transmissible in\u00a0vitro between cells of the central nervous system","volume":"148","author":"Sprenkle","year":"2019","journal-title":"J.\u00a0Neurochem."},{"key":"10.1016\/j.neuron.2019.12.014_bib39","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/2051-5960-1-31","article-title":"The unfolded protein response is activated in disease-affected brain regions in progressive supranuclear palsy and Alzheimer\u2019s disease","volume":"1","author":"Stutzbach","year":"2013","journal-title":"Acta Neuropathol. Commun."},{"key":"10.1016\/j.neuron.2019.12.014_bib40","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1126\/science.291.5504.657","article-title":"Control of synapse number by glia","volume":"291","author":"Ullian","year":"2001","journal-title":"Science"},{"key":"10.1016\/j.neuron.2019.12.014_bib41","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1212\/WNL.48.4.845","article-title":"A new leukoencephalopathy with vanishing white matter","volume":"48","author":"van der Knaap","year":"1997","journal-title":"Neurology"},{"key":"10.1016\/j.neuron.2019.12.014_bib42","doi-asserted-by":"crossref","first-page":"6391","DOI":"10.1523\/JNEUROSCI.6221-11.2012","article-title":"Genomic analysis of reactive astrogliosis","volume":"32","author":"Zamanian","year":"2012","journal-title":"J.\u00a0Neurosci."}],"container-title":["Neuron"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0896627319310566?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0896627319310566?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T07:24:02Z","timestamp":1760253842000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0896627319310566"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3]]},"references-count":42,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["S0896627319310566"],"URL":"https:\/\/doi.org\/10.1016\/j.neuron.2019.12.014","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.737167235.793571983","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.737167235.793571908","asserted-by":"object"}]},"ISSN":["0896-6273"],"issn-type":[{"value":"0896-6273","type":"print"}],"subject":[],"published":{"date-parts":[[2020,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Astrocyte Unfolded Protein Response Induces a Specific Reactivity State that Causes Non-Cell-Autonomous Neuronal Degeneration","name":"articletitle","label":"Article Title"},{"value":"Neuron","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.neuron.2019.12.014","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}