{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:29:28Z","timestamp":1787567368632,"version":"build-2736575974"},"reference-count":56,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mission Connect, a project of the TIRR Foundation"},{"id":[{"id":"https:\/\/ror.org\/017s9e951","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01NS112691"],"award-info":[{"award-number":["R01NS112691"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"award":["R01NS112691"],"award-info":[{"award-number":["R01NS112691"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01NS076708"],"award-info":[{"award-number":["R01NS076708"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"award":["R01NS076708"],"award-info":[{"award-number":["R01NS076708"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001641","name":"Glaucoma Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001641","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/05ez53b31","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R00EY029360"],"award-info":[{"award-number":["R00EY029360"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"award":["R00EY029360"],"award-info":[{"award-number":["R00EY029360"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Stress signaling is important for determining the fates of neurons following axonal insults. Previously, we showed that the stress-responsive kinase PERK contributes to injury-induced neurodegeneration (Larhammar et al., 2017). Here, we show that PERK acts primarily through activating transcription factor-4 (ATF4) to stimulate not only pro-apoptotic but also pro-regenerative responses following optic nerve damage. Using conditional knockout mice, we find an extensive PERK\/ATF4-dependent transcriptional response that includes canonical ATF4 target genes and modest contributions by C\/EBP Homologous Protein (CHOP). Overlap with c-Jun-dependent transcription suggests interplay with a parallel stress pathway that orchestrates regenerative and apoptotic responses. Accordingly, neuronal knockout of ATF4 recapitulates the neuroprotection afforded by PERK deficiency, and PERK or ATF4 knockout impairs optic axon regeneration enabled by disrupting the tumor suppressor PTEN. These findings reveal an integral role for PERK\/ATF4 in coordinating neurodegenerative and regenerative responses to CNS axon injury.<\/jats:p>","DOI":"10.7554\/elife.87528","type":"journal-article","created":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T08:47:53Z","timestamp":1684918073000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.87528","source":"Crossref","is-referenced-by-count":1,"title":["Coordinated stimulation of axon regenerative and neurodegenerative transcriptional programs by ATF4 following optic nerve injury"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2212-2071","authenticated-orcid":true,"given":"Preethi","family":"Somasundaram","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02pttbw34","id-type":"ROR","asserted-by":"publisher"}],"name":"Departments of Neurosurgery, Baylor College of Medicine","place":["Houston, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4852-2919","authenticated-orcid":true,"given":"Madeline M","family":"Farley","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02pttbw34","id-type":"ROR","asserted-by":"publisher"}],"name":"Departments of Neurosurgery, Baylor College of Medicine","place":["Houston, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0165-5669","authenticated-orcid":true,"given":"Melissa A","family":"Rudy","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02pttbw34","id-type":"ROR","asserted-by":"publisher"}],"name":"Departments of Neurosurgery, Baylor College of Medicine","place":["Houston, United States"]},{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Neuroimmunology and Glial Biology, Department of Neurology, University of California, San Francisco","place":["San Francisco, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2953-0440","authenticated-orcid":true,"given":"Katya","family":"Sigal","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Neuroimmunology and Glial Biology, Department of Neurology, University of California, San Francisco","place":["San Francisco, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4835-0849","authenticated-orcid":true,"given":"Andoni I","family":"Asencor","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Neuroimmunology and Glial Biology, Department of Neurology, University of California, San Francisco","place":["San Francisco, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4366-7645","authenticated-orcid":true,"given":"David G","family":"Stefanoff","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02pttbw34","id-type":"ROR","asserted-by":"publisher"}],"name":"Departments of Neurosurgery, Baylor College of Medicine","place":["Houston, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0284-3402","authenticated-orcid":true,"given":"Malay","family":"Shah","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02pttbw34","id-type":"ROR","asserted-by":"publisher"}],"name":"Departments of Neurosurgery, Baylor College of Medicine","place":["Houston, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5031-169X","authenticated-orcid":true,"given":"Puneetha","family":"Goli","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02pttbw34","id-type":"ROR","asserted-by":"publisher"}],"name":"Departments of Neurosurgery, Baylor College of Medicine","place":["Houston, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9773-071X","authenticated-orcid":true,"given":"Jenny","family":"Heo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02pttbw34","id-type":"ROR","asserted-by":"publisher"}],"name":"Departments of Neurosurgery, Baylor College of Medicine","place":["Houston, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2983-7453","authenticated-orcid":true,"given":"Shufang","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02pttbw34","id-type":"ROR","asserted-by":"publisher"}],"name":"Departments of Neurosurgery, Baylor College of Medicine","place":["Houston, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4213-3499","authenticated-orcid":true,"given":"Nicholas M","family":"Tran","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02pttbw34","id-type":"ROR","asserted-by":"publisher"}],"name":"Mol. and Human Genetics, Baylor College of Medicine","place":["Houston, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6723-3712","authenticated-orcid":true,"given":"Trent A","family":"Watkins","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02pttbw34","id-type":"ROR","asserted-by":"publisher"}],"name":"Departments of Neurosurgery, Baylor College of Medicine","place":["Houston, United States"]},{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Neuroimmunology and Glial Biology, Department of Neurology, University of California, San Francisco","place":["San Francisco, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.conb.2018.07.002","type":"journal-article","article-title":"An axonal stress response pathway: degenerative and regenerative signaling by DLK","volume":"53","author":"Asghari Adib","year":"2018","journal-title":"Current Opinion in Neurobiology"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1126\/science.aad0489","type":"journal-article","article-title":"mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle","volume":"351","author":"Ben-Sahra","year":"2016","journal-title":"Science"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"2317","DOI":"10.1242\/jcs.179127","type":"journal-article","article-title":"An initial phase of JNK activation inhibits cell death early in the endoplasmic reticulum stress response","volume":"129","author":"Brown","year":"2016","journal-title":"Journal of Cell Science"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"15878","DOI":"10.1074\/jbc.M114.635144","type":"journal-article","article-title":"Human CHAC1 protein degrades glutathione, and mRNA induction is regulated by the transcription factors ATF4 and ATF3 and a bipartite ATF\/CRE regulatory element","volume":"290","author":"Crawford","year":"2015","journal-title":"The Journal of Biological Chemistry"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.mcn.2018.08.001","type":"journal-article","article-title":"The effect of Jun dimerization on neurite outgrowth and motif binding","volume":"92","author":"Danzi","year":"2018","journal-title":"Molecular and Cellular Neurosciences"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"27290","DOI":"10.1074\/jbc.M112.374777","type":"journal-article","article-title":"Stress-induced skeletal muscle Gadd45a expression reprograms myonuclei and causes muscle atrophy","volume":"287","author":"Ebert","year":"2012","journal-title":"The Journal of Biological Chemistry"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.omtn.2023.07.015","type":"journal-article","article-title":"RGC-specific ATF4 and\/or CHOP deletion rescues glaucomatous neurodegeneration and visual function","volume":"33","author":"Fang","year":"2023","journal-title":"Molecular Therapy. Nucleic Acids"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1146\/annurev-pathol-012414-040354","type":"journal-article","article-title":"Intrinsic neuronal stress response pathways in injury and disease","volume":"13","author":"Farley","year":"2018","journal-title":"Annual Review of Pathology"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1080\/15384101.2015.1120929","type":"journal-article","article-title":"Mitochondrial dysfunction induces SESN2 gene expression through activating transcription factor 4","volume":"15","author":"Garaeva","year":"2016","journal-title":"Cell Cycle"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/ncb2738","type":"journal-article","article-title":"ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death","volume":"15","author":"Han","year":"2013","journal-title":"Nature Cell Biology"},{"key":"bib11","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006072","type":"journal-article","article-title":"Cell signaling and stress responses","volume":"8","author":"Hotamisligil","year":"2016","journal-title":"Cold Spring Harbor Perspectives in Biology"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/j.neuron.2011.11.026","type":"journal-article","article-title":"Differential effects of unfolded protein response pathways on axon injury-induced death of retinal ganglion cells","volume":"73","author":"Hu","year":"2012","journal-title":"Neuron"},{"key":"bib13","doi-asserted-by":"publisher","DOI":"10.48550\/arxiv.2210.04597","type":"preprint","article-title":"DeepVenn -- a web application for the creation of area-proportional venn diagrams using the deep learning framework tensorflow.Js","volume-title":"arXiv","author":"Hulsen","year":"2022"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"2625","DOI":"10.1016\/j.neuron.2022.06.002","type":"journal-article","article-title":"Overlapping transcriptional programs promote survival and axonal regeneration of injured retinal ganglion cells","volume":"110","author":"Jacobi","year":"2022","journal-title":"Neuron"},{"key":"bib15","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.61.2.31","type":"journal-article","article-title":"Activating Transcription Factor 3 (ATF3) protects retinal ganglion cells and promotes functional preservation after optic nerve crush","volume":"61","author":"Kole","year":"2020","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"bib16","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.20725","type":"journal-article","article-title":"Dual leucine zipper kinase-dependent PERK activation contributes to neuronal degeneration following insult","volume":"6","author":"Larhammar","year":"2017","journal-title":"eLife"},{"key":"bib17","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aag0394","type":"journal-article","article-title":"Loss of dual leucine zipper kinase signaling is protective in animal models of neurodegenerative disease","volume":"9","author":"Le Pichon","year":"2017","journal-title":"Science Translational Medicine"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1002\/gene.10036","type":"journal-article","article-title":"Cre\/loxP-mediated inactivation of the murine Pten tumor suppressor gene","volume":"32","author":"Lesche","year":"2002","journal-title":"Genesis"},{"key":"bib19","doi-asserted-by":"publisher","DOI":"10.3390\/genes11101165","type":"journal-article","article-title":"OneStopRNAseq: a web application for comprehensive and efficient analyses of RNA-Seq data","volume":"11","author":"Li","year":"2020","journal-title":"Genes"},{"key":"bib20","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.108777","type":"journal-article","article-title":"Optic nerve regeneration screen identifies multiple genes restricting adult neural repair","volume":"34","author":"Lindborg","year":"2021","journal-title":"Cell Reports"},{"key":"bib21","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00062","type":"journal-article","article-title":"Brain-derived neurotrophic factor elevates Activating Transcription Factor 4 (ATF4) in neurons and promotes ATF4-dependent induction of Sesn2","volume":"11","author":"Liu","year":"2018","journal-title":"Frontiers in Molecular Neuroscience"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/nn.2467","type":"journal-article","article-title":"A robust and high-throughput Cre reporting and characterization system for the whole mouse brain","volume":"13","author":"Madisen","year":"2010","journal-title":"Nature Neuroscience"},{"key":"bib23","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-022-00865-9","type":"journal-article","article-title":"Endoplasmic reticulum stress downregulates PGC-1\u03b1 in skeletal muscle through ATF4 and an mTOR-mediated reduction of CRTC2","volume":"20","author":"Montori-Grau","year":"2022","journal-title":"Cell Communication and Signaling"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/s11010-013-1663-1","type":"journal-article","article-title":"Transcriptional and post-translational regulation of mouse cation transport regulator homolog 1","volume":"380","author":"Oh-Hashi","year":"2013","journal-title":"Molecular and Cellular Biochemistry"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.15252\/embr.201642195","type":"journal-article","article-title":"The integrated stress response","volume":"17","author":"Pakos-Zebrucka","year":"2016","journal-title":"EMBO Reports"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1042\/BJ20061261","type":"journal-article","article-title":"Activation of the ATF3 gene through a co-ordinated amino acid-sensing response programme that controls transcriptional regulation of responsive genes following amino acid limitation","volume":"401","author":"Pan","year":"2007","journal-title":"The Biochemical Journal"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1016\/j.celrep.2017.04.042","type":"journal-article","article-title":"mTORC1 balances cellular amino acid supply with demand for protein synthesis through post-transcriptional control of ATF4","volume":"19","author":"Park","year":"2017","journal-title":"Cell Reports"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"33597","DOI":"10.1073\/pnas.2004683117","type":"journal-article","article-title":"Inhibition of GCK-IV kinases dissociates cell death and axon regeneration in CNS neurons","volume":"117","author":"Patel","year":"2020","journal-title":"PNAS"},{"key":"bib29","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00410","type":"journal-article","article-title":"Neurodegeneration: keeping ATF4 on a tight leash","volume":"11","author":"Pitale","year":"2017","journal-title":"Frontiers in Cellular Neuroscience"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.neuron.2004.06.005","type":"journal-article","article-title":"The AP-1 transcription factor c-Jun is required for efficient axonal regeneration","volume":"43","author":"Raivich","year":"2004","journal-title":"Neuron"},{"key":"bib31","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.68148","type":"journal-article","article-title":"Quantitative transportomics identifies Kif5a as a major regulator of neurodegeneration","volume":"11","author":"Shah","year":"2022","journal-title":"eLife"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1097\/WCO.0000000000000621","type":"journal-article","article-title":"Therapeutic opportunities and pitfalls in the treatment of axon degeneration","volume":"31","author":"Simon","year":"2018","journal-title":"Current Opinion in Neurology"},{"key":"bib33","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.338","type":"journal-article","article-title":"JUN is important for ocular hypertension-induced retinal ganglion cell degeneration","volume":"8","author":"Syc-Mazurek","year":"2017","journal-title":"Cell Death & Disease"},{"key":"bib34","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-017-0214-8","type":"journal-article","article-title":"Together JUN and DDIT3 (CHOP) control retinal ganglion cell death after axonal injury","volume":"12","author":"Syc-Mazurek","year":"2017","journal-title":"Molecular Neurodegeneration"},{"key":"bib35","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-04666-3","type":"journal-article","article-title":"Transcriptional control of retinal ganglion cell death after axonal injury","volume":"13","author":"Syc-Mazurek","year":"2022","journal-title":"Cell Death & Disease"},{"key":"bib36","doi-asserted-by":"publisher","DOI":"10.1101\/2023.07.13.548886","type":"preprint","article-title":"Single cell portal: an interactive home for single-cell genomics data","volume-title":"bioRxiv","author":"Tarhan","year":"2023"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"2607","DOI":"10.1016\/j.neuron.2022.06.003","type":"journal-article","article-title":"Core transcription programs controlling injury-induced neurodegeneration of retinal ganglion cells","volume":"110","author":"Tian","year":"2022","journal-title":"Neuron"},{"key":"bib38","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.01.008","type":"journal-article","article-title":"Core transcription programs controlling injury-induced neurodegeneration of retinal ganglion cells","volume":"111","author":"Tian","year":"2023","journal-title":"Neuron"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"2453","DOI":"10.1016\/j.neuron.2024.06.009","type":"journal-article","article-title":"Core transcription programs controlling injury-induced neurodegeneration of retinal ganglion cells","volume":"112","author":"Tian","year":"2024","journal-title":"Neuron"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1016\/j.neuron.2019.11.006","type":"journal-article","article-title":"Single-cell profiles of retinal ganglion cells differing in resilience to injury reveal neuroprotective genes","volume":"104","author":"Tran","year":"2019","journal-title":"Neuron"},{"key":"bib41","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2017.00235","type":"journal-article","article-title":"Shared and differential retinal responses against optic nerve injury and ocular hypertension","volume":"11","author":"Vidal-Sanz","year":"2017","journal-title":"Frontiers in Neuroscience"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.metabol.2012.07.017","type":"journal-article","article-title":"Effects of ATF4 on PGC1\u03b1 expression in brown adipose tissue and metabolic responses to cold stress","volume":"62","author":"Wang","year":"2013","journal-title":"Metabolism"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"3896","DOI":"10.1523\/JNEUROSCI.0102-20.2020","type":"journal-article","article-title":"Mouse \u03b3-Synuclein promoter-mediated gene expression and editing in mammalian retinal ganglion cells","volume":"40","author":"Wang","year":"2020","journal-title":"The Journal of Neuroscience"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"4039","DOI":"10.1073\/pnas.1211074110","type":"journal-article","article-title":"DLK initiates a transcriptional program that couples apoptotic and regenerative responses to axonal injury","volume":"110","author":"Watkins","year":"2013","journal-title":"PNAS"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"4045","DOI":"10.1073\/pnas.1211284110","type":"journal-article","article-title":"Functional genomic screening identifies dual leucine zipper kinase as a key mediator of retinal ganglion cell death","volume":"110","author":"Welsbie","year":"2013","journal-title":"PNAS"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1016\/j.neuron.2017.06.008","type":"journal-article","article-title":"Enhanced functional genomic screening identifies novel mediators of dual leucine zipper kinase-dependent injury signaling in neurons","volume":"94","author":"Welsbie","year":"2017","journal-title":"Neuron"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"5891","DOI":"10.1523\/JNEUROSCI.3709-15.2016","type":"journal-article","article-title":"Rescue of glaucomatous neurodegeneration by differentially modulating neuronal endoplasmic reticulum stress molecules","volume":"36","author":"Yang","year":"2016","journal-title":"The Journal of Neuroscience"},{"key":"bib48","doi-asserted-by":"publisher","DOI":"10.1038\/srep28736","type":"journal-article","article-title":"Transcriptome profiling of the rat retina after optic nerve transection","volume":"6","author":"Yasuda","year":"2016","journal-title":"Scientific Reports"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"3864","DOI":"10.1128\/MCB.22.11.3864-3874.2002","type":"journal-article","article-title":"The PERK eukaryotic initiation factor 2 alpha kinase is required for the development of the skeletal system, postnatal growth, and the function and viability of the pancreas","volume":"22","author":"Zhang","year":"2002","journal-title":"Molecular and Cellular Biology"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1016\/j.celrep.2015.12.053","type":"journal-article","article-title":"KDM4C and ATF4 cooperate in transcriptional control of amino acid metabolism","volume":"14","author":"Zhao","year":"2016","journal-title":"Cell Reports"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"1736","DOI":"10.1161\/CIRCRESAHA.116.305602","type":"journal-article","article-title":"C\/EBP-homologous protein (CHOP) in vascular smooth muscle cells regulates their proliferation in aortic explants and atherosclerotic lesions","volume":"116","author":"Zhou","year":"2015","journal-title":"Circulation Research"},{"key":"dataset1","type":"dataset","article-title":"Coordinated stimulation of axon regenerative and neurodegenerative transcriptional programs by Atf4 following optic nerve injury","volume-title":"NCBI Gene Expression Omnibus","author":"Somasundaram","year":"2023","unstructured":"Somasundaram P, Rudy MA, Tran NM, Watkins TA. 2023. Coordinated stimulation of axon regenerative and neurodegenerative transcriptional programs by Atf4 following optic nerve injury. NCBI Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE223321. GSE223321."},{"key":"dataset2","type":"dataset","article-title":"Characterization of chromatin accessibility changes in retinal ganglion cells (RGCs) following optic nerve crush","volume-title":"NCBI Gene Expression Omnibus","author":"Cheng","year":"2022","unstructured":"Cheng Y, Tian F, Geschwind D, He Z. 2022. Characterization of chromatin accessibility changes in retinal ganglion cells (RGCs) following optic nerve crush. NCBI Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE184547. GSE184547."},{"key":"dataset3","type":"dataset","article-title":"Core Transcription Programs Controlling Injury-Induced Neurodegeneration of Retinal Ganglion Cells","volume-title":"NCBI Gene Expression Omnibus","author":"Cheng","year":"2022","unstructured":"Cheng Y, Tian F, Geschwind D, He Z. 2022. Core Transcription Programs Controlling Injury-Induced Neurodegeneration of Retinal Ganglion Cells. NCBI Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE190667. GSE190667."},{"key":"dataset4","type":"dataset","article-title":"Transcriptional control of retinal ganglion cell death after axonal injury","volume-title":"NCBI Gene Expression Omnibus","author":"Syc-Mazurek","year":"2022","unstructured":"Syc-Mazurek SB, Yang HS, Marola OJ, Howell GR, Libby RT. 2022. Transcriptional control of retinal ganglion cell death after axonal injury. NCBI Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE168789. GSE168789."},{"key":"dataset5","type":"dataset","article-title":"Single-cell profiles of retinal neurons differing in resilience to injury reveal neuroprotective genes","volume-title":"NCBI Gene Expression Omnibus","author":"Tran","year":"2019","unstructured":"Tran NM, Shekhar K, Whitney IE, Jacobi A, Benhar I, Hong G, Yan W, Adiconis X, Arnold ME, Lee JM, Levin JZ, Lin D, Wang C, Lieber CM, Regev A, He Z, Sanes JR. 2019. Single-cell profiles of retinal neurons differing in resilience to injury reveal neuroprotective genes. NCBI Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE137400. GSE137400."}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/87528\/elife-87528-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/87528\/elife-87528-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/87528","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:07:05Z","timestamp":1787562425000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/87528"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,26]]},"references-count":56,"alternative-id":["10.7554\/eLife.87528"],"URL":"https:\/\/doi.org\/10.7554\/elife.87528","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.03.29.534798","asserted-by":"subject"}],"references":[{"id-type":"accession","id":"GSE184547","asserted-by":"subject"},{"id-type":"accession","id":"GSE190667","asserted-by":"subject"},{"id-type":"accession","id":"GSE168789","asserted-by":"subject"},{"id-type":"accession","id":"GSE137400","asserted-by":"subject"}],"is-same-as":[{"id-type":"doi","id":"10.7554\/eLife.87528.3","asserted-by":"subject"}],"is-version-of":[{"id-type":"doi","id":"10.7554\/eLife.87528.1","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.87528.2","asserted-by":"subject"}],"is-supplemented-by":[{"id-type":"accession","id":"GSE223321","asserted-by":"subject"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,26]]},"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":"RP87528"}}