{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T01:03:54Z","timestamp":1784077434372,"version":"3.55.0"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":68,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100002842","name":"Chiang Mai University","doi-asserted-by":"publisher","award":["FF66\/061"],"award-info":[{"award-number":["FF66\/061"]}],"id":[{"id":"10.13039\/501100002842","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002842","name":"Chiang Mai University","doi-asserted-by":"publisher","award":["FF67\/044"],"award-info":[{"award-number":["FF67\/044"]}],"id":[{"id":"10.13039\/501100002842","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002842","name":"Chiang Mai University","doi-asserted-by":"publisher","award":["FF68\/207569"],"award-info":[{"award-number":["FF68\/207569"]}],"id":[{"id":"10.13039\/501100002842","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010724","name":"Health Systems Research Institute","doi-asserted-by":"publisher","award":["66-124"],"award-info":[{"award-number":["66-124"]}],"id":[{"id":"10.13039\/501100010724","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010724","name":"Health Systems Research Institute","doi-asserted-by":"publisher","award":["68-060"],"award-info":[{"award-number":["68-060"]}],"id":[{"id":"10.13039\/501100010724","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"publisher","award":["N42A670768"],"award-info":[{"award-number":["N42A670768"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010731","name":"CMU | Faculty of Medicine, Chiang Mai University","doi-asserted-by":"publisher","award":["139\/2567"],"award-info":[{"award-number":["139\/2567"]}],"id":[{"id":"10.13039\/501100010731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"DOI":"10.1038\/s42003-026-10226-8","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T09:24:35Z","timestamp":1778232275000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of a pyrazolopyridine alkaloid that mitigates neuronal ER stress and age-related decline"],"prefix":"10.1038","volume":"9","author":[{"given":"Salinee","family":"Jantrapirom","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apiwat","family":"Sangphukieo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natsinee","family":"U-on","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8471-1165","authenticated-orcid":false,"given":"Pattaporn","family":"Poonsawas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wasinee","family":"Wongkumool","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranchana","family":"Yeewa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chansunee","family":"Panto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puttachat","family":"Poound","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7786-7698","authenticated-orcid":false,"given":"Ester","family":"Zito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Marrazza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0558-356X","authenticated-orcid":false,"given":"Luca","family":"Lo Piccolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"10226_CR1","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/sj.cdd.4401778","volume":"13","author":"D Lindholm","year":"2006","unstructured":"Lindholm, D., Wootz, H. & Korhonen, L. ER stress and neurodegenerative diseases. Cell Death Differ. 13, 385\u2013392 (2006).","journal-title":"Cell Death Differ."},{"key":"10226_CR2","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s13024-017-0183-y","volume":"12","author":"NT Sprenkle","year":"2017","unstructured":"Sprenkle, N. T., Sims, S. G., Sanchez, C. L. & Meares, G. P. Endoplasmic reticulum stress and inflammation in the central nervous system. Mol. Neurodegener. 12, 42 (2017).","journal-title":"Mol. Neurodegener."},{"key":"10226_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10495-016-1296-4","volume":"22","author":"C Xiang","year":"2017","unstructured":"Xiang, C., Wang, Y., Zhang, H. & Han, F. The role of endoplasmic reticulum stress in neurodegenerative disease. Apoptosis 22, 1\u201326 (2017).","journal-title":"Apoptosis"},{"key":"10226_CR4","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1038\/s41392-023-01570-w","volume":"8","author":"X Chen","year":"2023","unstructured":"Chen, X., Shi, C., He, M., Xiong, S. & Xia, X. Endoplasmic reticulum stress: molecular mechanism and therapeutic targets. Signal Transduct. Target Ther. 8, 352 (2023).","journal-title":"Signal Transduct. Target Ther."},{"key":"10226_CR5","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/S1097-2765(00)80018-0","volume":"1","author":"MG Pollard","year":"1998","unstructured":"Pollard, M. G., Travers, K. J. & Weissman, J. S. Ero1p: a novel and ubiquitous protein with an essential role in oxidative protein folding in the endoplasmic reticulum. Mol. Cell 1, 171\u2013182 (1998).","journal-title":"Mol. Cell"},{"key":"10226_CR6","doi-asserted-by":"publisher","first-page":"8400","DOI":"10.7150\/thno.45124","volume":"10","author":"J Zhang","year":"2020","unstructured":"Zhang, J. et al. Endoplasmic Reticulum stress-dependent expression of ERO1L promotes aerobic glycolysis in pancreatic cancer. Theranostics 10, 8400\u20138414 (2020).","journal-title":"Theranostics"},{"key":"10226_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111899","volume":"42","author":"A Bassot","year":"2023","unstructured":"Bassot, A. et al. The endoplasmic reticulum kinase PERK interacts with the oxidoreductase ERO1 to metabolically adapt mitochondria. Cell Rep. 42, 111899 (2023).","journal-title":"Cell Rep."},{"key":"10226_CR8","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1016\/j.molcel.2004.08.025","volume":"15","author":"CM Haynes","year":"2004","unstructured":"Haynes, C. M., Titus, E. A. & Cooper, A. A. Degradation of misfolded proteins prevents ER-derived oxidative stress and cell death. Mol. Cell 15, 767\u2013776 (2004).","journal-title":"Mol. Cell"},{"key":"10226_CR9","doi-asserted-by":"publisher","first-page":"3066","DOI":"10.1101\/gad.1250704","volume":"18","author":"SJ Marciniak","year":"2004","unstructured":"Marciniak, S. J. et al. CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes Dev. 18, 3066\u20133077 (2004).","journal-title":"Genes Dev."},{"key":"10226_CR10","doi-asserted-by":"publisher","first-page":"e56","DOI":"10.1371\/journal.pgen.0030056","volume":"3","author":"SP Curran","year":"2007","unstructured":"Curran, S. P. & Ruvkun, G. Lifespan regulation by evolutionarily conserved genes essential for viability. PLoS Genet. 3, e56 (2007).","journal-title":"PLoS Genet."},{"key":"10226_CR11","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2024.102674","volume":"242","author":"R Yeewa","year":"2024","unstructured":"Yeewa, R. et al. ERO1A inhibition mitigates neuronal ER stress and ameliorates UBQLN2(ALS) phenotypes in Drosophila melanogaster. Prog. Neurobiol. 242, 102674 (2024).","journal-title":"Prog. Neurobiol."},{"key":"10226_CR12","doi-asserted-by":"publisher","first-page":"23685","DOI":"10.1074\/jbc.M003061200","volume":"275","author":"M Pagani","year":"2000","unstructured":"Pagani, M. et al. Endoplasmic reticulum oxidoreductin 1-lbeta (ERO1-Lbeta), a human gene induced in the course of the unfolded protein response. J. Biol. Chem. 275, 23685\u201323692 (2000).","journal-title":"J. Biol. Chem."},{"key":"10226_CR13","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1083\/jcb.200911086","volume":"188","author":"E Zito","year":"2010","unstructured":"Zito, E., Chin, K. T., Blais, J., Harding, H. P. & Ron, D. ERO1-beta, a pancreas-specific disulfide oxidase, promotes insulin biogenesis and glucose homeostasis. J. Cell Biol. 188, 821\u2013832 (2010).","journal-title":"J. Cell Biol."},{"key":"10226_CR14","doi-asserted-by":"publisher","first-page":"20993","DOI":"10.1074\/jbc.M110.126599","volume":"285","author":"JD Blais","year":"2010","unstructured":"Blais, J. D. et al. A small molecule inhibitor of endoplasmic reticulum oxidation 1 (ERO1) with selectively reversible thiol reactivity. J. Biol. Chem. 285, 20993\u201321003 (2010).","journal-title":"J. Biol. Chem."},{"key":"10226_CR15","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-024-00736-1","volume":"8","author":"MA Voronkova","year":"2024","unstructured":"Voronkova, M. A. et al. ERO1A levels are a prognostic indicator in EGFR mutated non small cell lung cancer. NPJ Precis Oncol. 8, 250 (2024).","journal-title":"NPJ Precis Oncol."},{"key":"10226_CR16","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1016\/j.trecan.2022.06.006","volume":"8","author":"C Salvagno","year":"2022","unstructured":"Salvagno, C., Mandula, J. K., Rodriguez, P. C. & Cubillos-Ruiz, J. R. Decoding endoplasmic reticulum stress signals in cancer cells and antitumor immunity. Trends Cancer 8, 930\u2013943 (2022).","journal-title":"Trends Cancer"},{"key":"10226_CR17","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/s41573-021-00320-3","volume":"21","author":"SJ Marciniak","year":"2022","unstructured":"Marciniak, S. J., Chambers, J. E. & Ron, D. Pharmacological targeting of endoplasmic reticulum stress in disease. Nat. Rev. Drug Discov. 21, 115\u2013140 (2022).","journal-title":"Nat. Rev. Drug Discov."},{"key":"10226_CR18","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101439","volume":"5","author":"S Germani","year":"2024","unstructured":"Germani, S. et al. SEPN1-related myopathy depends on the oxidoreductase ERO1A and is druggable with the chemical chaperone TUDCA. Cell Rep. Med. 5, 101439 (2024).","journal-title":"Cell Rep. Med."},{"key":"10226_CR19","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1016\/j.bmc.2019.02.016","volume":"27","author":"KE Hayes","year":"2019","unstructured":"Hayes, K. E. et al. Inhibition of the FAD containing ER oxidoreductin 1 (Ero1) protein by EN-460 as a strategy for treatment of multiple myeloma. Bioorg. Med Chem. 27, 1479\u20131488 (2019).","journal-title":"Bioorg. Med Chem."},{"key":"10226_CR20","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1016\/S1097-2765(02)00696-2","volume":"10","author":"BP Tu","year":"2002","unstructured":"Tu, B. P. & Weissman, J. S. The FAD- and O(2)-dependent reaction cycle of Ero1-mediated oxidative protein folding in the endoplasmic reticulum. Mol. Cell 10, 983\u2013994 (2002).","journal-title":"Mol. Cell"},{"key":"10226_CR21","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.abb.2013.12.005","volume":"544","author":"MM Huijbers","year":"2014","unstructured":"Huijbers, M. M., Montersino, S., Westphal, A. H., Tischler, D. & van Berkel, W. J. Flavin dependent monooxygenases. Arch. Biochem. Biophys. 544, 2\u201317 (2014).","journal-title":"Arch. Biochem. Biophys."},{"key":"10226_CR22","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1021\/acsbiomedchemau.1c00062","volume":"2","author":"BD Johnson","year":"2022","unstructured":"Johnson, B. D. et al. Identification of Natural Product Sulfuretin Derivatives as Inhibitors for the Endoplasmic Reticulum Redox Protein ERO1alpha. ACS Bio Med. Chem. Au 2, 161\u2013170 (2022).","journal-title":"ACS Bio Med. Chem. Au"},{"key":"10226_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-025-07426-1","volume":"16","author":"E Varone","year":"2025","unstructured":"Varone, E. et al. Small molecule-mediated inhibition of the oxidoreductase ERO1A restrains aggressive breast cancer by impairing VEGF and PD-L1 in the tumor microenvironment. Cell Death Dis. 16, 105 (2025).","journal-title":"Cell Death Dis."},{"key":"10226_CR24","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1038\/s41573-020-00114-z","volume":"20","author":"AG Atanasov","year":"2021","unstructured":"Atanasov, A. G., Zotchev, S. B. & Dirsch, V. M. International Natural Product Sciences, T. & Supuran, C. T. Natural products in drug discovery: advances and opportunities. Nat. Rev. Drug Discov. 20, 200\u2013216 (2021).","journal-title":"Nat. Rev. Drug Discov."},{"key":"10226_CR25","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1080\/17460441.2025.2507382","volume":"20","author":"S Xie","year":"2025","unstructured":"Xie, S., Zhan, F., Zhu, J., Xu, S. & Xu, J. The latest advances with natural products in drug discovery and opportunities for the future: a 2025 update. Expert Opin. Drug Discov. 20, 827\u2013843 (2025).","journal-title":"Expert Opin. Drug Discov."},{"key":"10226_CR26","doi-asserted-by":"publisher","first-page":"445","DOI":"10.5483\/BMBRep.2015.48.8.099","volume":"48","author":"HD Ryoo","year":"2015","unstructured":"Ryoo, H. D. Drosophila as a model for unfolded protein response research. BMB Rep. 48, 445\u2013453 (2015).","journal-title":"BMB Rep."},{"key":"10226_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-2039-6","volume":"10","author":"C Yan","year":"2019","unstructured":"Yan, C. et al. IRE1 promotes neurodegeneration through autophagy-dependent neuron death in the Drosophila model of Parkinson\u2019s disease. Cell Death Dis. 10, 800 (2019).","journal-title":"Cell Death Dis."},{"key":"10226_CR28","doi-asserted-by":"publisher","unstructured":"Katsube, H., Hinami, Y., Yamazoe, T. & Inoue, Y. H. Endoplasmic reticulum stress-induced cellular dysfunction and cell death in insulin-producing cells results in diabetes-like phenotypes in Drosophila. Biol Open 8, https:\/\/doi.org\/10.1242\/bio.046524 (2019).","DOI":"10.1242\/bio.046524"},{"key":"10226_CR29","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/nature10353","volume":"477","author":"HX Deng","year":"2011","unstructured":"Deng, H. X. et al. Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS\/dementia. Nature 477, 211\u2013215 (2011).","journal-title":"Nature"},{"key":"10226_CR30","doi-asserted-by":"publisher","first-page":"15230","DOI":"10.1073\/pnas.1917371117","volume":"117","author":"JJ Wu","year":"2020","unstructured":"Wu, J. J. et al. ALS\/FTD mutations in UBQLN2 impede autophagy by reducing autophagosome acidification through loss of function. Proc. Natl. Acad. Sci. USA. 117, 15230\u201315241 (2020).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10226_CR31","doi-asserted-by":"publisher","first-page":"3859","DOI":"10.1007\/s00018-019-03394-w","volume":"77","author":"M Halloran","year":"2020","unstructured":"Halloran, M. et al. Amyotrophic lateral sclerosis-linked UBQLN2 mutants inhibit endoplasmic reticulum to Golgi transport, leading to Golgi fragmentation and ER stress. Cell Mol. Life Sci. 77, 3859\u20133873 (2020).","journal-title":"Cell Mol. Life Sci."},{"key":"10226_CR32","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s40478-019-0758-7","volume":"7","author":"L Renaud","year":"2019","unstructured":"Renaud, L., Picher-Martel, V., Codron, P. & Julien, J. P. Key role of UBQLN2 in pathogenesis of amyotrophic lateral sclerosis and frontotemporal dementia. Acta Neuropathol. Commun. 7, 103 (2019).","journal-title":"Acta Neuropathol. Commun."},{"key":"10226_CR33","doi-asserted-by":"publisher","unstructured":"Torrence, M. E. et al. The mTORC1-mediated activation of ATF4 promotes protein and glutathione synthesis downstream of growth signals. Elife 10, https:\/\/doi.org\/10.7554\/eLife.63326 (2021).","DOI":"10.7554\/eLife.63326"},{"key":"10226_CR34","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1126\/science.aad0489","volume":"351","author":"I Ben-Sahra","year":"2016","unstructured":"Ben-Sahra, I., Hoxhaj, G., Ricoult, S. J. H., Asara, J. M. & Manning, B. D. mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle. Science 351, 728\u2013733 (2016).","journal-title":"Science"},{"key":"10226_CR35","doi-asserted-by":"publisher","unstructured":"Hetz, C. & Dillin, A. Central role of the ER proteostasis network in healthy aging. Trends Cell Biol. https:\/\/doi.org\/10.1016\/j.tcb.2024.10.003 (2024).","DOI":"10.1016\/j.tcb.2024.10.003"},{"key":"10226_CR36","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","volume":"153","author":"C Lopez-Otin","year":"2013","unstructured":"Lopez-Otin, C., Blasco, M. A., Partridge, L., Serrano, M. & Kroemer, G. The hallmarks of aging. Cell 153, 1194\u20131217 (2013).","journal-title":"Cell"},{"key":"10226_CR37","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/s12276-021-00560-8","volume":"53","author":"KR Bhattarai","year":"2021","unstructured":"Bhattarai, K. R., Riaz, T. A., Kim, H. R. & Chae, H. J. The aftermath of the interplay between the endoplasmic reticulum stress response and redox signaling. Exp. Mol. Med. 53, 151\u2013167 (2021).","journal-title":"Exp. Mol. Med."},{"key":"10226_CR38","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.freeradbiomed.2022.01.006","volume":"180","author":"X Qiao","year":"2022","unstructured":"Qiao, X. et al. ER reductive stress caused by Ero1alpha S-nitrosation accelerates senescence. Free Radic. Biol. Med. 180, 165\u2013178 (2022).","journal-title":"Free Radic. Biol. Med"},{"key":"10226_CR39","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1007\/s10522-019-09837-y","volume":"20","author":"KF Azman","year":"2019","unstructured":"Azman, K. F. & Zakaria, R. D-Galactose-induced accelerated aging model: an overview. Biogerontology 20, 763\u2013782 (2019).","journal-title":"Biogerontology"},{"key":"10226_CR40","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.exger.2017.10.029","volume":"101","author":"T Shwe","year":"2018","unstructured":"Shwe, T., Pratchayasakul, W., Chattipakorn, N. & Chattipakorn, S. C. Role of D-galactose-induced brain aging and its potential used for therapeutic interventions. Exp. Gerontol. 101, 13\u201336 (2018).","journal-title":"Exp. Gerontol."},{"key":"10226_CR41","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.neurobiolaging.2024.10.002","volume":"144","author":"R Yeewa","year":"2024","unstructured":"Yeewa, R. et al. The histone acylation reader ENL\/AF9 regulates aging in Drosophila melanogaster. Neurobiol. Aging 144, 153\u2013162 (2024).","journal-title":"Neurobiol. Aging"},{"key":"10226_CR42","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbas.2023.100077","volume":"3","author":"SK Pai","year":"2023","unstructured":"Pai, S. K. Mechanisms underlying fragmented sleep in aging. Aging Brain 3, 100077 (2023).","journal-title":"Aging Brain"},{"key":"10226_CR43","doi-asserted-by":"publisher","unstructured":"Salazar, A. M., Aparicio, R., Clark, R. I., Rera, M. & Walker, D. W. Intestinal barrier dysfunction: an evolutionarily conserved hallmark of aging. Dis. Model Mech. 16, https:\/\/doi.org\/10.1242\/dmm.049969 (2023).","DOI":"10.1242\/dmm.049969"},{"key":"10226_CR44","doi-asserted-by":"publisher","first-page":"21528","DOI":"10.1073\/pnas.1215849110","volume":"109","author":"M Rera","year":"2012","unstructured":"Rera, M., Clark, R. I. & Walker, D. W. Intestinal barrier dysfunction links metabolic and inflammatory markers of aging to death in Drosophila. Proc. Natl. Acad. Sci. USA. 109, 21528\u201321533 (2012).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10226_CR45","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05153-5","volume":"13","author":"A Ajoolabady","year":"2022","unstructured":"Ajoolabady, A., Lindholm, D., Ren, J. & Pratico, D. ER stress and UPR in Alzheimer\u2019s disease: mechanisms, pathogenesis, treatments. Cell Death Dis. 13, 706 (2022).","journal-title":"Cell Death Dis."},{"key":"10226_CR46","doi-asserted-by":"publisher","first-page":"3911","DOI":"10.1128\/MCB.00980-14","volume":"34","author":"GP Meares","year":"2014","unstructured":"Meares, G. P. et al. PERK-dependent activation of JAK1 and STAT3 contributes to endoplasmic reticulum stress-induced inflammation. Mol. Cell Biol. 34, 3911\u20133925 (2014).","journal-title":"Mol. Cell Biol."},{"key":"10226_CR47","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.1038\/cdd.2014.111","volume":"21","author":"S Bellani","year":"2014","unstructured":"Bellani, S. et al. GRP78 clustering at the cell surface of neurons transduces the action of exogenous alpha-synuclein. Cell Death Differ. 21, 1971\u20131983 (2014).","journal-title":"Cell Death Differ."},{"key":"10226_CR48","doi-asserted-by":"publisher","first-page":"107525","DOI":"10.1016\/j.pharmthera.2020.107525","volume":"210","author":"AG Shergalis","year":"2020","unstructured":"Shergalis, A. G., Hu, S., Bankhead, A. 3rd & Neamati, N. Role of the ERO1-PDI interaction in oxidative protein folding and disease. Pharm. Ther. 210, 107525 (2020).","journal-title":"Pharm. Ther."},{"key":"10226_CR49","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1089\/ars.2021.0018","volume":"35","author":"V Jha","year":"2021","unstructured":"Jha, V. et al. ERO1-PDI redox signaling in health and disease. Antioxid. Redox Signal 35, 1093\u20131115 (2021).","journal-title":"Antioxid. Redox Signal"},{"key":"10226_CR50","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1248\/bpb.32.1043","volume":"32","author":"M Yamazaki","year":"2009","unstructured":"Yamazaki, M., Chiba, K. & Yoshikawa, C. Genipin suppresses A23187-induced cytotoxicity in neuro2a cells. Biol. Pharm. Bull. 32, 1043\u20131046 (2009).","journal-title":"Biol. Pharm. Bull."},{"key":"10226_CR51","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.1111\/bph.13449","volume":"173","author":"ZG Ma","year":"2016","unstructured":"Ma, Z. G. et al. Protection against cardiac hypertrophy by geniposide involves the GLP-1 receptor\/AMPKalpha signalling pathway. Br. J. Pharm. 173, 1502\u20131516 (2016).","journal-title":"Br. J. Pharm."},{"key":"10226_CR52","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1111\/cbdd.14098","volume":"100","author":"D Atukuri","year":"2022","unstructured":"Atukuri, D. Pyrazolopyridine: An efficient pharmacophore in recent drug design and development. Chem. Biol. Drug Des. 100, 376\u2013388 (2022).","journal-title":"Chem. Biol. Drug Des."},{"key":"10226_CR53","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115880","volume":"262","author":"OM Waly","year":"2023","unstructured":"Waly, O. M., El-Sayed, S. M., Ghaly, M. A. & El-Subbagh, H. I. Multi-targeted anti-Alzheimer\u2019s agents: Synthesis, biological evaluation, and molecular modeling study of some pyrazolopyridine hybrids. Eur. J. Med. Chem. 262, 115880 (2023).","journal-title":"Eur. J. Med. Chem."},{"key":"10226_CR54","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.111893","volume":"186","author":"Z Zhao","year":"2020","unstructured":"Zhao, Z. et al. Pyrazolone structural motif in medicinal chemistry: Retrospect and prospect. Eur. J. Med. Chem. 186, 111893 (2020).","journal-title":"Eur. J. Med. Chem."},{"key":"10226_CR55","doi-asserted-by":"publisher","first-page":"1753","DOI":"10.1517\/14656566.2010.493558","volume":"11","author":"PA Lapchak","year":"2010","unstructured":"Lapchak, P. A. A critical assessment of edaravone acute ischemic stroke efficacy trials: is edaravone an effective neuroprotective therapy? Expert Opin. Pharmacother. 11, 1753\u20131763 (2010).","journal-title":"Expert Opin. Pharmacother."},{"key":"10226_CR56","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2025.108037","volume":"222","author":"M Retini","year":"2025","unstructured":"Retini, M. et al. Pyrazolone-based ERO1 inhibitors in ERO1-driven triple-negative breast cancer and SEPN1-related myopathy: Structure-activity relationship and therapeutic potential. Pharm. Res. 222, 108037 (2025).","journal-title":"Pharm. Res."},{"key":"10226_CR57","doi-asserted-by":"publisher","first-page":"W296","DOI":"10.1093\/nar\/gky427","volume":"46","author":"A Waterhouse","year":"2018","unstructured":"Waterhouse, A. et al. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. 46, W296\u2013W303 (2018).","journal-title":"Nucleic Acids Res."},{"key":"10226_CR58","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s13321-019-0358-3","volume":"11","author":"PJ Ropp","year":"2019","unstructured":"Ropp, P. J. et al. Gypsum-DL: an open-source program for preparing small-molecule libraries for structure-based virtual screening. J. Cheminform. 11, 34 (2019).","journal-title":"J. Cheminform."},{"key":"10226_CR59","doi-asserted-by":"publisher","first-page":"2785","DOI":"10.1002\/jcc.21256","volume":"30","author":"GM Morris","year":"2009","unstructured":"Morris, G. M. et al. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J. Comput. Chem. 30, 2785\u20132791 (2009).","journal-title":"J. Comput. Chem."},{"key":"10226_CR60","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/jcc.21334","volume":"31","author":"O Trott","year":"2010","unstructured":"Trott, O. & Olson, A. J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31, 455\u2013461 (2010).","journal-title":"J. Comput. Chem."},{"key":"10226_CR61","doi-asserted-by":"publisher","DOI":"10.1111\/jfbc.12987","volume":"43","author":"C Kiriya","year":"2019","unstructured":"Kiriya, C., Yeewa, R., Khanaree, C. & Chewonarin, T. Purple rice extract inhibits testosterone-induced rat prostatic hyperplasia and growth of human prostate cancer cell line by reduction of androgen receptor activation. J. Food Biochem. 43, e12987 (2019).","journal-title":"J. Food Biochem."},{"key":"10226_CR62","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1016\/S0891-5849(98)00315-3","volume":"26","author":"R Re","year":"1999","unstructured":"Re, R. et al. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic. Biol. Med. 26, 1231\u20131237 (1999).","journal-title":"Free Radic. Biol. Med."},{"key":"10226_CR63","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1242\/dev.118.2.401","volume":"118","author":"AH Brand","year":"1993","unstructured":"Brand, A. H. & Perrimon, N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401\u2013415 (1993).","journal-title":"Development"},{"key":"10226_CR64","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2023.102558","volume":"233","author":"L Lo Piccolo","year":"2024","unstructured":"Lo Piccolo, L. et al. FAME4-associating YEATS2 knockdown impairs dopaminergic synaptic integrity and leads to seizure-like behaviours in Drosophila melanogaster. Prog. Neurobiol. 233, 102558 (2024).","journal-title":"Prog. Neurobiol."},{"key":"10226_CR65","doi-asserted-by":"publisher","first-page":"3038","DOI":"10.1016\/j.bbadis.2018.06.017","volume":"1864","author":"S Jantrapirom","year":"2018","unstructured":"Jantrapirom, S., Lo Piccolo, L., Yoshida, H. & Yamaguchi, M. Depletion of Ubiquilin induces an augmentation in soluble ubiquitinated Drosophila TDP-43 to drive neurotoxicity in the fly. Biochim. Biophys. Acta Mol. Basis Dis. 1864, 3038\u20133049 (2018).","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"10226_CR66","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.expneurol.2017.03.011","volume":"292","author":"L Lo Piccolo","year":"2017","unstructured":"Lo Piccolo, L. & Yamaguchi, M. RNAi of arcRNA hsromega affects sub-cellular localization of Drosophila FUS to drive neurodiseases. Exp. Neurol. 292, 125\u2013134 (2017).","journal-title":"Exp. Neurol."},{"key":"10226_CR67","doi-asserted-by":"publisher","unstructured":"Jantrapirom S., et al. Discovery of a pyrazolopyridine alkaloid that mitigates neuronal ER stress and age-related decline [Data set]. figshare. https:\/\/doi.org\/10.6084\/m9.figshare.32087106 (2026).","DOI":"10.6084\/m9.figshare.32087106"}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-10226-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-10226-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-10226-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:04:00Z","timestamp":1784073840000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-10226-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,8]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["10226"],"URL":"https:\/\/doi.org\/10.1038\/s42003-026-10226-8","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.07.14.664722","asserted-by":"object"}]},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,8]]},"assertion":[{"value":"2 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests. The funders had no role in the design of the study, the collection\/analysis\/interpretation of data, or the decision to submit the manuscript.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"964"}}