{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T04:58:26Z","timestamp":1791781106078,"version":"4.3.4"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000016","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["MOST 111-2628-B-039- 006-MY3"],"award-info":[{"award-number":["MOST 111-2628-B-039- 006-MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007300","name":"China Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007300","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012544","name":"China Medical University","doi-asserted-by":"publisher","award":["CMU113-MF-06"],"award-info":[{"award-number":["CMU113-MF-06"]}],"id":[{"id":"10.13039\/501100012544","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neurobiology of Disease"],"published-print":{"date-parts":[[2025,8]]},"DOI":"10.1016\/j.nbd.2025.106992","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T02:34:02Z","timestamp":1749090842000},"page":"106992","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"special_numbering":"C","title":["Sigma-1R\u2013Pom121 axis preserves nuclear transport and integrity in poly-PR-induced C9orf72 ALS"],"prefix":"10.1016","volume":"212","author":[{"given":"Chun-Yu","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsuan-Cheng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru-Huei","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddie Feng-Ju","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Chi","family":"Hsieh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsung-Ping","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiang-En","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Ming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.nbd.2025.106992_bb0005","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1038\/s41556-022-00927-7","article-title":"Mechanical force application to the nucleus regulates nucleocytoplasmic transport","volume":"24","author":"Andreu","year":"2022","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.nbd.2025.106992_bb0010","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.molcel.2004.12.010","article-title":"The integral membrane nucleoporin pom121 functionally links nuclear pore complex assembly and nuclear envelope formation","volume":"17","author":"Antonin","year":"2005","journal-title":"Mol. Cell"},{"key":"10.1016\/j.nbd.2025.106992_bb0015","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.semcdb.2017.06.026","article-title":"Floppy but not sloppy: interaction mechanism of FG-nucleoporins and nuclear transport receptors","volume":"68","author":"Aramburu","year":"2017","journal-title":"Semin. Cell Dev. Biol."},{"key":"10.1016\/j.nbd.2025.106992_bb0020","doi-asserted-by":"crossref","DOI":"10.26508\/lsa.202402853","article-title":"Activation of the Keap1\/Nrf2 pathway suppresses mitochondrial dysfunction, oxidative stress, and motor phenotypes in C9orf72 ALS\/FTD models","volume":"7","author":"Au","year":"2024","journal-title":"Life Sci. Alliance"},{"key":"10.1016\/j.nbd.2025.106992_bb0025","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1007\/s00415-013-7231-5","article-title":"Cortisol levels and the severity and outcomes of acute stroke: a systematic review","volume":"261","author":"Barugh","year":"2014","journal-title":"J. Neurol."},{"key":"10.1016\/j.nbd.2025.106992_bb0030","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1186\/s40478-023-01648-0","article-title":"A toxic gain-of-function mechanism in C9orf72 ALS impairs the autophagy-lysosome pathway in neurons","volume":"11","author":"Beckers","year":"2023","journal-title":"Acta Neuropathol. Commun."},{"key":"10.1016\/j.nbd.2025.106992_bb0035","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/s42004-021-00547-6","article-title":"Nanoscopic investigation of C9orf72 poly-GA oligomers on nuclear membrane disruption by a photoinducible platform","volume":"4","author":"Chien","year":"2021","journal-title":"Commun. Chem."},{"key":"10.1016\/j.nbd.2025.106992_bb0040","doi-asserted-by":"crossref","first-page":"R368","DOI":"10.1016\/S0960-9822(98)70239-8","article-title":"Nucleocytoplasmic transport: driving and directing transport","volume":"8","author":"Cole","year":"1998","journal-title":"Curr. Biol."},{"key":"10.1016\/j.nbd.2025.106992_bb0045","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/j.neuron.2020.06.027","article-title":"G(4)C(2) repeat RNA initiates a POM121-mediated reduction in specific nucleoporins in C9orf72 ALS\/FTD","volume":"107","author":"Coyne","year":"2020","journal-title":"Neuron"},{"key":"10.1016\/j.nbd.2025.106992_bb0050","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.nbd.2019.05.009","article-title":"Pridopidine protects neurons from mutant-huntingtin toxicity via the sigma-1 receptor","volume":"129","author":"Eddings","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.nbd.2025.106992_bb0055","doi-asserted-by":"crossref","DOI":"10.1155\/2010\/214074","article-title":"Cellular stress responses: cell survival and cell death","volume":"2010","author":"Fulda","year":"2010","journal-title":"Int. J. Cell Biol."},{"key":"10.1016\/j.nbd.2025.106992_bb0060","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abq3215","article-title":"Poly(ADP-ribose) promotes toxicity of C9ORF72 arginine-rich dipeptide repeat proteins","volume":"14","author":"Gao","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.nbd.2025.106992_bb0065","doi-asserted-by":"crossref","first-page":"3827","DOI":"10.1038\/s41467-019-11837-y","article-title":"Modulation of actin polymerization affects nucleocytoplasmic transport in multiple forms of amyotrophic lateral sclerosis","volume":"10","author":"Giampetruzzi","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.nbd.2025.106992_bb0070","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1038\/s41593-019-0396-1","article-title":"Toxic expanded GGGGCC repeat transcription is mediated by the PAF1 complex in C9orf72-associated FTD","volume":"22","author":"Goodman","year":"2019","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.nbd.2025.106992_bb0075","doi-asserted-by":"crossref","first-page":"2906","DOI":"10.1038\/s41467-019-10956-w","article-title":"Motor dysfunction and neurodegeneration in a C9orf72 mouse line expressing poly-PR","volume":"10","author":"Hao","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.nbd.2025.106992_bb0080","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.51685","article-title":"C9orf72 arginine-rich dipeptide repeat proteins disrupt karyopherin-mediated nuclear import","volume":"9","author":"Hayes","year":"2020","journal-title":"Elife"},{"key":"10.1016\/j.nbd.2025.106992_bb0085","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2020.108538","article-title":"Nuclear import receptors directly bind to arginine-rich dipeptide repeat proteins and suppress their pathological interactions","volume":"33","author":"Hutten","year":"2020","journal-title":"Cell Rep."},{"key":"10.1016\/j.nbd.2025.106992_bb0090","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-022-25732-y","article-title":"Molecular basis of C9orf72 poly-PR interference with the beta-karyopherin family of nuclear transport receptors","volume":"12","author":"Jafarinia","year":"2022","journal-title":"Sci. Rep."},{"key":"10.1016\/j.nbd.2025.106992_bb0095","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.89694","article-title":"C9orf72 polyPR directly binds to various nuclear transport components","volume":"12","author":"Jafarinia","year":"2024","journal-title":"Elife"},{"key":"10.1016\/j.nbd.2025.106992_bb0100","doi-asserted-by":"crossref","first-page":"3562","DOI":"10.1038\/s41380-022-01545-3","article-title":"Fluvoxamine and long COVID-19; a new role for sigma-1 receptor (S1R) agonists","volume":"27","author":"Khani","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"10.1016\/j.nbd.2025.106992_bb0105","doi-asserted-by":"crossref","first-page":"5707","DOI":"10.1007\/s00018-021-03872-0","article-title":"DNA damage as a mechanism of neurodegeneration in ALS and a contributor to astrocyte toxicity","volume":"78","author":"Kok","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.nbd.2025.106992_bb0110","doi-asserted-by":"crossref","first-page":"5580","DOI":"10.1038\/s41467-020-19396-3","article-title":"Sigma-1 receptor chaperones rescue nucleocytoplasmic transport deficit seen in cellular and Drosophila ALS\/FTD models","volume":"11","author":"Lee","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.nbd.2025.106992_bb0115","doi-asserted-by":"crossref","first-page":"5282","DOI":"10.1007\/s12035-023-03885-9","article-title":"Fluvoxamine exerts sigma-1R to rescue autophagy via Pom121-mediated nucleocytoplasmic transport of TFEB","volume":"61","author":"Lin","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.nbd.2025.106992_bb0120","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.neuron.2016.09.015","article-title":"Poly(GR) in C9ORF72-related ALS\/FTD compromises mitochondrial function and increases oxidative stress and DNA damage in iPSC-derived motor neurons","volume":"92","author":"Lopez-Gonzalez","year":"2016","journal-title":"Neuron"},{"key":"10.1016\/j.nbd.2025.106992_bb0125","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1475-9268-1-2","article-title":"MG-132, an inhibitor of proteasomes and calpains, induced inhibition of oocyte maturation and aneuploidy in mouse oocytes","volume":"1","author":"Mailhes","year":"2002","journal-title":"Cell Chromosome"},{"key":"10.1016\/j.nbd.2025.106992_bb0130","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/978-3-319-50174-1_10","article-title":"Sigma-1 receptors and neurodegenerative diseases: towards a hypothesis of Sigma-1 receptors as amplifiers of neurodegeneration and neuroprotection","volume":"964","author":"Nguyen","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.nbd.2025.106992_bb0135","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.bmc.2018.12.022","article-title":"Tripeptide analogues of MG132 as protease inhibitors","volume":"27","author":"Pehere","year":"2019","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.nbd.2025.106992_bb0140","doi-asserted-by":"crossref","first-page":"R551","DOI":"10.1016\/S0960-9822(01)00340-2","article-title":"Nucleocytoplasmic transport: diffusion channel or phase transition?","volume":"11","author":"Rabut","year":"2001","journal-title":"Curr. Biol."},{"key":"10.1016\/j.nbd.2025.106992_bb0145","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.neuron.2011.09.010","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":"10.1016\/j.nbd.2025.106992_bb0150","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1016\/j.cell.2018.07.015","article-title":"Nuclear pores promote lethal prostate cancer by increasing POM121-driven E2F1, MYC, and AR nuclear import","volume":"174","author":"Rodriguez-Bravo","year":"2018","journal-title":"Cell"},{"key":"10.1016\/j.nbd.2025.106992_bb0155","doi-asserted-by":"crossref","first-page":"7911","DOI":"10.1523\/JNEUROSCI.5313-06.2007","article-title":"ATF3 increases the intrinsic growth state of DRG neurons to enhance peripheral nerve regeneration","volume":"27","author":"Seijffers","year":"2007","journal-title":"J. Neurosci."},{"key":"10.1016\/j.nbd.2025.106992_bb0160","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.nbd.2007.12.002","article-title":"Protective effects of heat shock protein 27 in a model of ALS occur in the early stages of disease progression","volume":"30","author":"Sharp","year":"2008","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.nbd.2025.106992_bb0165","doi-asserted-by":"crossref","first-page":"E1111","DOI":"10.1073\/pnas.1620293114","article-title":"Toxic PR(n) poly-dipeptides encoded by the C9orf72 repeat expansion block nuclear import and export","volume":"114","author":"Shi","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.nbd.2025.106992_bb0170","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s40478-016-0324-5","article-title":"The ALS\/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to regulate the autophagy-lysosome pathway","volume":"4","author":"Sullivan","year":"2016","journal-title":"Acta Neuropathol. Commun."},{"key":"10.1016\/j.nbd.2025.106992_bb0175","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1080\/15548627.2022.2063003","article-title":"Nucleoporin POM121 signals TFEB-mediated autophagy via activation of SIGMAR1\/sigma-1 receptor chaperone by pridopidine","volume":"19","author":"Wang","year":"2023","journal-title":"Autophagy"},{"key":"10.1016\/j.nbd.2025.106992_bb0180","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s12929-017-0380-6","article-title":"Roles of sigma-1 receptors on mitochondrial functions relevant to neurodegenerative diseases","volume":"24","author":"Weng","year":"2017","journal-title":"J. Biomed. Sci."},{"key":"10.1016\/j.nbd.2025.106992_bb0185","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1016\/j.apsb.2024.02.004","article-title":"ALS-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating BCL2-BECN1 interaction","volume":"14","author":"Xu","year":"2024","journal-title":"Acta Pharm. Sin. B"},{"key":"10.1016\/j.nbd.2025.106992_bb0190","doi-asserted-by":"crossref","first-page":"4700","DOI":"10.1038\/s41388-019-0745-2","article-title":"Inhibition of karyopherin beta 1 suppresses prostate cancer growth","volume":"38","author":"Yang","year":"2019","journal-title":"Oncogene"},{"key":"10.1016\/j.nbd.2025.106992_bb0195","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/s41392-023-01649-4","article-title":"Nuclear transport proteins: structure, function, and disease relevance","volume":"8","author":"Yang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.nbd.2025.106992_bb0200","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41419-023-06371-1","article-title":"Nuclear pore protein POM121 regulates subcellular localization and transcriptional activity of PPARgamma","volume":"15","author":"Yu","year":"2024","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.nbd.2025.106992_bb0205","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nature14973","article-title":"The C9orf72 repeat expansion disrupts nucleocytoplasmic transport","volume":"525","author":"Zhang","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.nbd.2025.106992_bb0210","article-title":"Acidic pH environment induces autophagy in osteoblasts","volume":"7","author":"Zhang","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.nbd.2025.106992_bb0215","first-page":"2050","article-title":"Silver nanoparticles compromise female embryonic stem cell differentiation through disturbing X chromosome inactivation","volume":"13","author":"Zhang","year":"2019","journal-title":"ACS Nano"},{"key":"10.1016\/j.nbd.2025.106992_bb0220","doi-asserted-by":"crossref","DOI":"10.1126\/science.aav2606","article-title":"Heterochromatin anomalies and double-stranded RNA accumulation underlie C9orf72 poly(PR) toxicity","volume":"363","author":"Zhang","year":"2019","journal-title":"Science"},{"key":"10.1016\/j.nbd.2025.106992_bb0225","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1093\/jnen\/nlad078","article-title":"C9orf72 proline-arginine dipeptide repeats disrupt the proteasome and perturb proteolytic activities","volume":"82","author":"Zhang","year":"2023","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"10.1016\/j.nbd.2025.106992_bb0230","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.1038\/s41388-018-0180-9","article-title":"KPNB1 inhibition disrupts proteostasis and triggers unfolded protein response-mediated apoptosis in glioblastoma cells","volume":"37","author":"Zhu","year":"2018","journal-title":"Oncogene"}],"container-title":["Neurobiology of Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0969996125002086?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0969996125002086?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T13:12:59Z","timestamp":1762348379000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0969996125002086"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":46,"alternative-id":["S0969996125002086"],"URL":"https:\/\/doi.org\/10.1016\/j.nbd.2025.106992","relation":{},"ISSN":["0969-9961"],"issn-type":[{"value":"0969-9961","type":"print"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Sigma-1R\u2013Pom121 axis preserves nuclear transport and integrity in poly-PR-induced C9orf72 ALS","name":"articletitle","label":"Article Title"},{"value":"Neurobiology of Disease","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.nbd.2025.106992","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"106992"}}