{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:30:23Z","timestamp":1790947823705,"version":"4.1.0"},"reference-count":70,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T00:00:00Z","timestamp":1705276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T00:00:00Z","timestamp":1705276800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T00:00:00Z","timestamp":1705276800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["346986"],"award-info":[{"award-number":["346986"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["628389"],"award-info":[{"award-number":["628389"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS110385"],"award-info":[{"award-number":["R01NS110385"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS079702"],"award-info":[{"award-number":["R01NS079702"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R21NS090912"],"award-info":[{"award-number":["R21NS090912"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["RF1AG057882"],"award-info":[{"award-number":["RF1AG057882"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS109150"],"award-info":[{"award-number":["R01NS109150"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Family Strong for ALS"},{"name":"Farber Family Foundation"}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss. Importantly, non-neuronal cell types such as astrocytes also play significant roles in disease pathogenesis. However, mechanisms of astrocyte contribution to ALS remain incompletely understood. Astrocyte involvement suggests that transcellular signaling may play a role in disease. We examined contribution of transmembrane signaling molecule ephrinB2 to ALS pathogenesis, in particular its role in driving motor neuron damage by spinal cord astrocytes. In symptomatic SOD1\n                    <jats:sup>G93A<\/jats:sup>\n                    mice (a well-established ALS model), ephrinB2 expression was dramatically increased in ventral horn astrocytes. Reducing ephrinB2 in the cervical spinal cord ventral horn via viral-mediated shRNA delivery reduced motor neuron loss and preserved respiratory function by maintaining phrenic motor neuron innervation of diaphragm. EphrinB2 expression was also elevated in human ALS spinal cord. These findings implicate ephrinB2 upregulation as both a transcellular signaling mechanism in mutant SOD1-associated ALS and a promising therapeutic target.\n                  <\/jats:p>","DOI":"10.7554\/elife.89298","type":"journal-article","created":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T10:31:54Z","timestamp":1689589914000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.89298","source":"Crossref","is-referenced-by-count":5,"title":["EphrinB2 knockdown in cervical spinal cord preserves diaphragm innervation in a mutant SOD1 mouse model of ALS"],"prefix":"10.7554","volume":"12","author":[{"given":"Mark W","family":"Urban","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00ysqcn41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuroscience, Jefferson Synaptic Biology Center, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College at Thomas Jefferson University","place":["Philadelphia, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Brittany A","family":"Charsar","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00ysqcn41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuroscience, Jefferson Synaptic Biology Center, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College at Thomas Jefferson University","place":["Philadelphia, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Nicolette M","family":"Heinsinger","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00ysqcn41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuroscience, Jefferson Synaptic Biology Center, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College at Thomas Jefferson University","place":["Philadelphia, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"},{"role":"software","vocabulary":"credit"}]},{"given":"Shashirekha S","family":"Markandaiah","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00ysqcn41","id-type":"ROR","asserted-by":"publisher"}],"name":"Jefferson Weinberg ALS Center, Department of Neuroscience, Vickie and Jack Farber Institute for Neuroscience, Thomas Jefferson University","place":["Philadelphia, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Lindsay","family":"Sprimont","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00ysqcn41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuroscience, Jefferson Synaptic Biology Center, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College at Thomas Jefferson University","place":["Philadelphia, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00ysqcn41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuroscience, Jefferson Synaptic Biology Center, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College at Thomas Jefferson University","place":["Philadelphia, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Eric V","family":"Brown","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00ysqcn41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuroscience, Jefferson Synaptic Biology Center, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College at Thomas Jefferson University","place":["Philadelphia, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Nathan T","family":"Henderson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00ysqcn41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuroscience, Jefferson Synaptic Biology Center, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College at Thomas Jefferson University","place":["Philadelphia, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Samantha J","family":"Thomas","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00ysqcn41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuroscience, Jefferson Synaptic Biology Center, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College at Thomas Jefferson University","place":["Philadelphia, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Biswarup","family":"Ghosh","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00ysqcn41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuroscience, Jefferson Synaptic Biology Center, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College at Thomas Jefferson University","place":["Philadelphia, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Rachel E","family":"Cain","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00ysqcn41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuroscience, Jefferson Synaptic Biology Center, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College at Thomas Jefferson University","place":["Philadelphia, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"},{"role":"software","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6338-6404","authenticated-orcid":true,"given":"Davide","family":"Trotti","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00ysqcn41","id-type":"ROR","asserted-by":"publisher"}],"name":"Jefferson Weinberg ALS Center, Department of Neuroscience, Vickie and Jack Farber Institute for Neuroscience, Thomas Jefferson University","place":["Philadelphia, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Piera","family":"Pasinelli","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00ysqcn41","id-type":"ROR","asserted-by":"publisher"}],"name":"Jefferson Weinberg ALS Center, Department of Neuroscience, Vickie and Jack Farber Institute for Neuroscience, Thomas Jefferson University","place":["Philadelphia, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Megan C","family":"Wright","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00ff4bt20","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, Arcadia University","place":["Glenside, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Matthew B","family":"Dalva","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00ysqcn41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuroscience, Jefferson Synaptic Biology Center, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College at Thomas Jefferson University","place":["Philadelphia, United States"]},{"id":[{"id":"https:\/\/ror.org\/04vmvtb21","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Cell and Molecular Biology, Tulane Brain Institute, Tulane University","place":["New Orleans, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5956-6135","authenticated-orcid":true,"given":"Angelo C","family":"Lepore","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00ysqcn41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuroscience, Jefferson Synaptic Biology Center, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College at Thomas Jefferson University","place":["Philadelphia, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2024,1,15]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22691-2","type":"journal-article","article-title":"Single nucleus RNA-sequencing defines unexpected diversity of cholinergic neuron types in the adult mouse spinal cord","volume":"12","author":"Alkaslasi","year":"2021","journal-title":"Nature Communications"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1093\/brain\/120.10.1723","type":"journal-article","article-title":"Phenotypic heterogeneity in motor neuron disease patients with CuZn-superoxide dismutase mutations in Scandinavia","volume":"120 ( Pt 10)","author":"Andersen","year":"1997","journal-title":"Brain"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1038\/s41593-020-00795-0","type":"journal-article","article-title":"Single-cell transcriptomic analysis of the adult mouse spinal cord reveals molecular diversity of autonomic and skeletal motor neurons","volume":"24","author":"Blum","year":"2021","journal-title":"Nature Neuroscience"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1146\/annurev.neuro.27.070203.144244","type":"journal-article","article-title":"Unraveling the mechanisms involved in motor neuron degeneration in ALS","volume":"27","author":"Bruijn","year":"2004","journal-title":"Annual Review of Neuroscience"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"7789","DOI":"10.1523\/JNEUROSCI.23-21-07789.2003","type":"journal-article","article-title":"Ephrin-B2 and EphB2 regulation of astrocyte-meningeal fibroblast interactions in response to spinal cord lesions in adult rats","volume":"23","author":"Bundesen","year":"2003","journal-title":"The Journal of Neuroscience"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"4115","DOI":"10.1523\/JNEUROSCI.5308-07.2008","type":"journal-article","article-title":"Mitochondrial dysfunction in SOD1G93A-bearing astrocytes promotes motor neuron degeneration: prevention by mitochondrial-targeted antioxidants","volume":"28","author":"Cassina","year":"2008","journal-title":"The Journal of Neuroscience"},{"key":"bib7","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2020.105153","type":"journal-article","article-title":"LAR inhibitory peptide promotes recovery of diaphragm function and multiple forms of respiratory neural circuit plasticity after cervical spinal cord injury","volume":"147","author":"Cheng","year":"2021","journal-title":"Neurobiology of Disease"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.neuron.2011.09.011","type":"journal-article","article-title":"Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS","volume":"72","author":"DeJesus-Hernandez","year":"2011","journal-title":"Neuron"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1111\/j.1460-9568.2006.04704.x","type":"journal-article","article-title":"Accumulation of the inhibitory receptor EphA4 may prevent regeneration of corticospinal tract axons following lesion","volume":"23","author":"Fabes","year":"2006","journal-title":"The European Journal of Neuroscience"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1002\/glia.22936","type":"journal-article","article-title":"GLT1 overexpression reverses established neuropathic pain-related behavior and attenuates chronic dorsal horn neuron activation following cervical spinal cord injury","volume":"64","author":"Falnikar","year":"2016","journal-title":"Glia"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1146\/annurev.neuro.21.1.309","type":"journal-article","article-title":"The ephrins and Eph receptors in neural development","volume":"21","author":"Flanagan","year":"1998","journal-title":"Annual Review of Neuroscience"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"5982","DOI":"10.1523\/JNEUROSCI.3084-17.2018","type":"journal-article","article-title":"Local bdnf delivery to the injured cervical spinal cord using an engineered hydrogel enhances diaphragmatic respiratory function","volume":"38","author":"Ghosh","year":"2018","journal-title":"The Journal of Neuroscience"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1016\/j.nbd.2019.04.014","type":"journal-article","article-title":"A hydrogel engineered to deliver minocycline locally to the injured cervical spinal cord protects respiratory neural circuitry and preserves diaphragm function","volume":"127","author":"Ghosh","year":"2019","journal-title":"Neurobiology of Disease"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1002\/glia.23555","type":"journal-article","article-title":"Astrocyte progenitor transplantation promotes regeneration of bulbospinal respiratory axons, recovery of diaphragm function, and a reduced macrophage response following cervical spinal cord injury","volume":"67","author":"Goul\u00e3o","year":"2019","journal-title":"Glia"},{"key":"bib15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2002457","type":"journal-article","article-title":"Extracellular phosphorylation of a receptor tyrosine kinase controls synaptic localization of NMDA receptors and regulates pathological pain","volume":"15","author":"Hanamura","year":"2017","journal-title":"PLOS Biology"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.mcn.2018.07.002","type":"journal-article","article-title":"EphBs and ephrin-Bs: Trans-synaptic organizers of synapse development and function","volume":"91","author":"Henderson","year":"2018","journal-title":"Molecular and Cellular Neurosciences"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1083\/jcb.200908164","type":"journal-article","article-title":"Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond","volume":"187","author":"Ilieva","year":"2009","journal-title":"The Journal of Cell Biology"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1007\/s10495-018-1458-7","type":"journal-article","article-title":"Dying to communicate: apoptotic functions of Eph\/Ephrin proteins","volume":"23","author":"Kandouz","year":"2018","journal-title":"Apoptosis"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/nn.2231","type":"journal-article","article-title":"Bidirectional modulation of synaptic functions by Eph\/ephrin signaling","volume":"12","author":"Klein","year":"2009","journal-title":"Nature Neuroscience"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.expneurol.2005.02.020","type":"journal-article","article-title":"Lineage-restricted neural precursors survive, migrate, and differentiate following transplantation into the injured adult spinal cord","volume":"194","author":"Lepore","year":"2005","journal-title":"Experimental Neurology"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.brainres.2007.09.034","type":"journal-article","article-title":"Intraparenchymal spinal cord delivery of adeno-associated virus IGF-1 is protective in the SOD1G93A model of ALS","volume":"1185","author":"Lepore","year":"2007","journal-title":"Brain Research"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/j.expneurol.2008.02.020","type":"journal-article","article-title":"Selective ablation of proliferating astrocytes does not affect disease outcome in either acute or chronic models of motor neuron degeneration","volume":"211","author":"Lepore","year":"2008","journal-title":"Experimental Neurology"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1038\/nn.2210","type":"journal-article","article-title":"Focal transplantation-based astrocyte replacement is neuroprotective in a model of motor neuron disease","volume":"11","author":"Lepore","year":"2008","journal-title":"Nature Neuroscience"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.nbd.2010.03.021","type":"journal-article","article-title":"Peripheral hyperstimulation alters site of disease onset and course in SOD1 rats","volume":"39","author":"Lepore","year":"2010","journal-title":"Neurobiology of Disease"},{"key":"bib25","doi-asserted-by":"publisher","DOI":"10.3791\/3069","type":"journal-article","article-title":"Intraspinal cell transplantation for targeting cervical ventral horn in amyotrophic lateral sclerosis and traumatic spinal cord injury","volume":"55","author":"Lepore","year":"2011","journal-title":"Journal of Visualized Experiments"},{"key":"bib26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025968","type":"journal-article","article-title":"Human glial-restricted progenitor transplantation into cervical spinal cord of the SOD1 mouse model of ALS","volume":"6","author":"Lepore","year":"2011","journal-title":"PLOS ONE"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.neulet.2012.04.060","type":"journal-article","article-title":"Inhibition of EphA4 signaling after ischemia-reperfusion reduces apoptosis of CA1 pyramidal neurons","volume":"518","author":"Li","year":"2012","journal-title":"Neuroscience Letters"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"7622","DOI":"10.1523\/JNEUROSCI.4690-13.2014","type":"journal-article","article-title":"Overexpression of the astrocyte glutamate transporter GLT1 exacerbates phrenic motor neuron degeneration, diaphragm compromise, and forelimb motor dysfunction following cervical contusion spinal cord injury","volume":"34","author":"Li","year":"2014","journal-title":"The Journal of Neuroscience"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1038\/mt.2014.236","type":"journal-article","article-title":"Transplantation of glial progenitors that overexpress glutamate transporter GLT1 preserves diaphragm function following cervical SCI","volume":"23","author":"Li","year":"2015","journal-title":"Molecular Therapy"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.nbd.2015.03.010","type":"journal-article","article-title":"GLT1 overexpression in SOD1(G93A) mouse cervical spinal cord does not preserve diaphragm function or extend disease","volume":"78","author":"Li","year":"2015","journal-title":"Neurobiology of Disease"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/j.expneurol.2015.07.020","type":"journal-article","article-title":"Human iPS cell-derived astrocyte transplants preserve respiratory function after spinal cord injury","volume":"271","author":"Li","year":"2015","journal-title":"Experimental Neurology"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.nbd.2018.03.002","type":"journal-article","article-title":"Antisense-mediated reduction of EphA4 in the adult CNS does not improve the function of mice with amyotrophic lateral sclerosis","volume":"114","author":"Ling","year":"2018","journal-title":"Neurobiology of Disease"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.nbd.2005.06.019","type":"journal-article","article-title":"Degeneration of respiratory motor neurons in the SOD1 G93A transgenic rat model of ALS","volume":"21","author":"Llad\u00f3","year":"2006","journal-title":"Neurobiology of Disease"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1002\/ana.21147","type":"journal-article","article-title":"Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations","volume":"61","author":"Mackenzie","year":"2007","journal-title":"Annals of Neurology"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1002\/jgm.860","type":"journal-article","article-title":"Stable RNA interference: Comparison of U6 and H1 promoters in endothelial cells and in mouse brain","volume":"8","author":"M\u00e4kinen","year":"2006","journal-title":"The Journal of Gene Medicine"},{"key":"bib36","doi-asserted-by":"publisher","DOI":"10.3791\/52605","type":"journal-article","article-title":"Functional and morphological assessment of diaphragm innervation by phrenic motor neurons","volume":"99","author":"Martin","year":"2015","journal-title":"Journal of Visualized Experiments"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"20487","DOI":"10.1073\/pnas.0811862106","type":"journal-article","article-title":"Ephrin-B1 and ephrin-B2 mediate EphB-dependent presynaptic development via syntenin-1","volume":"106","author":"McClelland","year":"2009","journal-title":"PNAS"},{"key":"bib38","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2022.851563","type":"journal-article","article-title":"Breached barriers: A scoping review of blood-central nervous system barrier pathology in amyotrophic lateral sclerosis","volume":"16","author":"Mirian","year":"2022","journal-title":"Frontiers in Cellular Neuroscience"},{"key":"bib39","volume-title":"Amyotrophic lateral sclerosis","author":"Mitsumoto","year":"1998","type":"book"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/nn994","type":"journal-article","article-title":"Control of hippocampal dendritic spine morphology through ephrin-A3\/EphA4 signaling","volume":"6","author":"Murai","year":"2003","journal-title":"Nature Neuroscience"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.expneurol.2012.03.007","type":"journal-article","article-title":"Phrenic motor neuron degeneration compromises phrenic axonal circuitry and diaphragm activity in a unilateral cervical contusion model of spinal cord injury","volume":"235","author":"Nicaise","year":"2012","journal-title":"Experimental Neurology"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"2748","DOI":"10.1089\/neu.2012.2467","type":"journal-article","article-title":"Degeneration of phrenic motor neurons induces long-term diaphragm deficits following mid-cervical spinal contusion in mice","volume":"29","author":"Nicaise","year":"2012","journal-title":"Journal of Neurotrauma"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1089\/neu.2012.2728","type":"journal-article","article-title":"Early phrenic motor neuron loss and transient respiratory abnormalities after unilateral cervical spinal cord contusion","volume":"30","author":"Nicaise","year":"2013","journal-title":"Journal of Neurotrauma"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"5353","DOI":"10.1523\/JNEUROSCI.0282-11.2011","type":"journal-article","article-title":"EphB controls NMDA receptor function and synaptic targeting in a subunit-specific manner","volume":"31","author":"Nolt","year":"2011","journal-title":"The Journal of Neuroscience"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/0925-4773(95)00461-0","type":"journal-article","article-title":"The receptor tyrosine kinase, Cek8, is transiently expressed on subtypes of motoneurons in the spinal cord during development","volume":"54","author":"Ohta","year":"1996","journal-title":"Mechanisms of Development"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.cell.2008.03.011","type":"journal-article","article-title":"Eph-ephrin bidirectional signaling in physiology and disease","volume":"133","author":"Pasquale","year":"2008","journal-title":"Cell"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1002\/glia.20207","type":"journal-article","article-title":"Astrocyte activation and reactive gliosis","volume":"50","author":"Pekny","year":"2005","journal-title":"Glia"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"E756","DOI":"10.1073\/pnas.1222361110","type":"journal-article","article-title":"Intricate interplay between astrocytes and motor neurons in ALS","volume":"110","author":"Phatnani","year":"2013","journal-title":"PNAS"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1021\/cb500413n","type":"journal-article","article-title":"Dynamic principle for designing antagonistic\/agonistic molecules for EphA4 receptor, the only known ALS modifier","volume":"10","author":"Qin","year":"2015","journal-title":"ACS Chemical Biology"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1136\/jnnp.61.6.565","type":"journal-article","article-title":"Cu\/Zn superoxide dismutase gene mutations in amyotrophic lateral sclerosis: Correlation between genotype and clinical features","volume":"61","author":"Radunov\u00edc","year":"1996","journal-title":"Journal of Neurology, Neurosurgery, and Psychiatry"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.neuron.2011.09.010","type":"journal-article","article-title":"A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD","volume":"72","author":"Renton","year":"2011","journal-title":"Neuron"},{"key":"bib52","doi-asserted-by":"publisher","DOI":"10.1038\/364362c0","type":"journal-article","article-title":"Mutations in Cu\/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis","volume":"364","author":"Rosen","year":"1993","journal-title":"Nature"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/ana.410380114","type":"journal-article","article-title":"Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis","volume":"38","author":"Rothstein","year":"1995","journal-title":"Annals of Neurology"},{"key":"bib54","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-019-0759-6","type":"journal-article","article-title":"Reduction of ephrin-A5 aggravates disease progression in amyotrophic lateral sclerosis","volume":"7","author":"Ru\u00e9","year":"2019","journal-title":"Acta Neuropathologica Communications"},{"key":"bib55","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-50615-0","type":"journal-article","article-title":"Reducing EphA4 before disease onset does not affect survival in a mouse model of amyotrophic lateral sclerosis","volume":"9","author":"Ru\u00e9","year":"2019","journal-title":"Scientific Reports"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.pneurobio.2009.05.004","type":"journal-article","article-title":"Axon guidance proteins: Novel therapeutic targets for ALS?","volume":"88","author":"Schmidt","year":"2009","journal-title":"Progress in Neurobiology"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"11452","DOI":"10.1074\/jbc.M116.774141","type":"journal-article","article-title":"Identification and characterization of nanobodies targeting the EphA4 receptor","volume":"292","author":"Schoonaert","year":"2017","journal-title":"The Journal of Biological Chemistry"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1016\/j.cell.2008.04.039","type":"journal-article","article-title":"The amyotrophic lateral sclerosis 8 protein VAPB is cleaved, secreted, and acts as a ligand for Eph receptors","volume":"133","author":"Tsuda","year":"2008","journal-title":"Cell"},{"key":"bib59","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01283-z","type":"journal-article","article-title":"A neuroprotective astrocyte state is induced by neuronal signal EphB1 but fails in ALS models","volume":"8","author":"Tyzack","year":"2017","journal-title":"Nature Communications"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1016\/j.tins.2021.04.008","type":"journal-article","article-title":"Non-cell-autonomous pathogenic mechanisms in amyotrophic lateral sclerosis","volume":"44","author":"Van Harten","year":"2021","journal-title":"Trends in Neurosciences"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1038\/nm.2901","type":"journal-article","article-title":"EPHA4 is a disease modifier of amyotrophic lateral sclerosis in animal models and in humans","volume":"18","author":"Van Hoecke","year":"2012","journal-title":"Nature Medicine"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/B978-0-444-63488-7.00010-0","type":"journal-article","article-title":"The challenges of respiratory motor system recovery following cervical spinal cord injury","volume":"212","author":"Warren","year":"2014","journal-title":"Progress in Brain Research"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/cne.21439","type":"journal-article","article-title":"Distinct patterns of motor nerve terminal sprouting induced by ciliary neurotrophic factor vs. botulinum toxin","volume":"504","author":"Wright","year":"2007","journal-title":"The Journal of Comparative Neurology"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/j.expneurol.2007.03.011","type":"journal-article","article-title":"Ciliary neurotrophic factor is not required for terminal sprouting and compensatory reinnervation of neuromuscular synapses: Re-evaluation of CNTF null mice","volume":"205","author":"Wright","year":"2007","journal-title":"Experimental Neurology"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"14942","DOI":"10.1523\/JNEUROSCI.2276-09.2009","type":"journal-article","article-title":"Distinct muscarinic acetylcholine receptor subtypes contribute to stability and growth, but not compensatory plasticity, of neuromuscular synapses","volume":"29","author":"Wright","year":"2009","journal-title":"The Journal of Neuroscience"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.chembiol.2017.01.006","type":"journal-article","article-title":"Potent and selective epha4 agonists for the treatment of als","volume":"24","author":"Wu","year":"2017","journal-title":"Cell Chemical Biology"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/nn2047","type":"journal-article","article-title":"Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis","volume":"11","author":"Yamanaka","year":"2008","journal-title":"Nature Neuroscience"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.neures.2017.09.011","type":"journal-article","article-title":"The multi-dimensional roles of astrocytes in ALS","volume":"126","author":"Yamanaka","year":"2018","journal-title":"Neuroscience Research"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.neuroscience.2017.01.038","type":"journal-article","article-title":"The identification of a novel isoform of EphA4 and ITS expression in SOD1G93A mice","volume":"347","author":"Zhao","year":"2017","journal-title":"Neuroscience"},{"key":"bib70","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-29845-1","type":"journal-article","article-title":"Decreased signalling of EphA4 improves functional performance and motor neuron survival in the SOD1G93A ALS mouse model","volume":"8","author":"Zhao","year":"2018","journal-title":"Scientific Reports"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/89298\/elife-89298-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/89298\/elife-89298-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/89298","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:46:07Z","timestamp":1787568367000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/89298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,15]]},"references-count":70,"alternative-id":["10.7554\/eLife.89298"],"URL":"https:\/\/doi.org\/10.7554\/elife.89298","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.05.10.538887","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2023.05.10.538887","asserted-by":"object"}],"is-same-as":[{"id-type":"doi","id":"10.7554\/eLife.89298.4","asserted-by":"subject"}],"is-version-of":[{"id-type":"doi","id":"10.7554\/eLife.89298.1","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.89298.2","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.89298.3","asserted-by":"subject"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,15]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"RP89298"}}