{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:21:45Z","timestamp":1787008905798,"version":"build-2736575974"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"4","funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS077284"],"award-info":[{"award-number":["R01NS077284"]}],"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":["R01NS070899"],"award-info":[{"award-number":["R01NS070899"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01 BX002149"],"award-info":[{"award-number":["I01 BX002149"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AA027074"],"award-info":[{"award-number":["R01 AA027074"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["I01 BX002978"],"award-info":[{"award-number":["I01 BX002978"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ochanomizu University Scholarship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Frontotemporal dementia (FTD) is an early onset dementia characterized by progressive atrophy of the frontal and\/or temporal lobes. FTD is highly heritable with mutations in progranulin accounting for 5\u201326% of cases in different populations. Progranulin is involved in endocytosis, secretion and lysosomal processes, but its functions under physiological and pathological conditions remains to be defined. Many FTD-causing non-sense progranulin mutations contain a premature termination codon (PTC), thus progranulin haploinsufficiency has been proposed as a major disease mechanism. Currently, there is no effective FTD treatment or therapy. Aminoglycosides are a class of antibiotics that possess a less-known function to induce eukaryotic ribosomal readthrough of PTCs to produce a full-length protein. The aminoglycoside-induced readthrough strategy has been utilized to treat multiple human diseases caused by PTCs. In this study, we tested the only clinically approved readthrough small molecule PTC124 and 11 aminoglycosides in a cell culture system on four PTCs responsible for FTD or a related neurodegenerative disease amyotrophic lateral sclerosis. We found that the aminoglycosides G418 and gentamicin rescued the expression of the progranulin R493X mutation. G418 was more effective than gentamicin (~50% rescue versus &amp;lt;10%), and the effect was dose- and time-dependent. The progranulin readthrough protein displayed similar subcellular localization as the wild-type progranulin protein. These data provide an exciting proof-of-concept that aminoglycosides or other readthrough-promoting compounds are a therapeutic avenue for familial FTD caused by progranulin PTC mutations.<\/jats:p>","DOI":"10.1093\/hmg\/ddz280","type":"journal-article","created":{"date-parts":[[2019,11,21]],"date-time":"2019-11-21T15:10:23Z","timestamp":1574349023000},"page":"624-634","source":"Crossref","is-referenced-by-count":21,"title":["Frontotemporal dementia non-sense mutation of progranulin rescued by aminoglycosides"],"prefix":"10.1093","volume":"29","author":[{"given":"Lisha","family":"Kuang","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Hashimoto","sequence":"first","affiliation":[{"name":"Department of Pathology, University of California, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pathology, University of California, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew S","family":"Gentry","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haining","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA"},{"name":"Lexington VA Medical Center, Research & Development, Lexington, KY 40502, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,1,8]]},"reference":[{"key":"2020031303072457700_ref1","doi-asserted-by":"crossref","first-page":"3091","DOI":"10.1093\/brain\/awl267","article-title":"Progranulin gene mutations associated with frontotemporal dementia and progressive non-fluent aphasia","volume":"129","author":"Snowden","year":"2006","journal-title":"Brain"},{"key":"2020031303072457700_ref2","doi-asserted-by":"crossref","first-page":"817","DOI":"10.3109\/07853890.2012.665471","article-title":"The molecular basis of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum","volume":"44","author":"Van Langenhove","year":"2012","journal-title":"Ann. 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Mol. Genet."},{"key":"2020031303072457700_ref9","doi-asserted-by":"crossref","first-page":"3081","DOI":"10.1093\/brain\/awx198","article-title":"Progranulin: a new avenue towards the understanding and treatment of neurodegenerative disease","volume":"140","author":"Chitramuthu","year":"2017","journal-title":"Brain"},{"key":"2020031303072457700_ref10","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/nm816","article-title":"Progranulin is a mediator of the wound response","volume":"9","author":"He","year":"2003","journal-title":"Nat. Med."},{"key":"2020031303072457700_ref11","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1742-2094-4-7","article-title":"Progranulin in frontotemporal lobar degeneration and neuroinflammation","volume":"4","author":"Ahmed","year":"2007","journal-title":"J. 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Genomics Hum. Genet."},{"key":"2020031303072457700_ref29","doi-asserted-by":"crossref","first-page":"355","DOI":"10.3892\/ijmm.2014.1809","article-title":"Therapeutic suppression of premature termination codons: mechanisms and clinical considerations (review)","volume":"34","author":"Karijolich","year":"2014","journal-title":"Int. J. Mol. Med."},{"key":"2020031303072457700_ref30","first-page":"37","article-title":"Clinical potential of ataluren in the treatment of Duchenne muscular dystrophy","volume":"6","author":"Namgoong","year":"2016","journal-title":"Degener. Neurol. Neuromuscul. Dis."},{"key":"2020031303072457700_ref31","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1001\/archneurol.2011.53","article-title":"Genetic and clinical features of progranulin-associated frontotemporal lobar degeneration","volume":"68","author":"Chen-Plotkin","year":"2011","journal-title":"Arch. Neurol."},{"key":"2020031303072457700_ref32","doi-asserted-by":"crossref","first-page":"3038","DOI":"10.1073\/pnas.1424127112","article-title":"Nonsense suppression by near-cognate tRNAs employs alternative base pairing at codon positions 1 and 3","volume":"112","author":"Roy","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2020031303072457700_ref33","doi-asserted-by":"crossref","first-page":"C723","DOI":"10.1152\/ajpcell.00462.2010","article-title":"A practical guide to evaluating colocalization in biological microscopy","volume":"300","author":"Dunn","year":"2011","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2020031303072457700_ref34","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.neuron.2010.09.034","article-title":"Sortilin-mediated endocytosis determines levels of the frontotemporal dementia protein, progranulin","volume":"68","author":"Hu","year":"2010","journal-title":"Neuron"},{"key":"2020031303072457700_ref35","doi-asserted-by":"crossref","first-page":"3350","DOI":"10.1093\/nar\/gkq1277","article-title":"Rescue of non-sense mutated p53 tumor suppressor gene by aminoglycosides","volume":"39","author":"Floquet","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"2020031303072457700_ref36","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1080\/15476286.2017.1285480","article-title":"Characterization of new-generation aminoglycoside promoting premature termination codon readthrough in cancer cells","volume":"14","author":"Bidou","year":"2017","journal-title":"RNA Biol."},{"key":"2020031303072457700_ref37","doi-asserted-by":"crossref","first-page":"4160","DOI":"10.1093\/hmg\/ddq335","article-title":"Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules","volume":"19","author":"Bosco","year":"2010","journal-title":"Hum. 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Alzheimers Dis."},{"key":"2020031303072457700_ref41","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1212\/WNL.0b013e3181ccc732","article-title":"Genetic contribution of FUS to frontotemporal lobar degeneration","volume":"74","author":"Van Langenhove","year":"2010","journal-title":"Neurology"},{"key":"2020031303072457700_ref42","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1136\/jmg.2011.089615","article-title":"Efficiency of translation termination in humans is highly dependent upon nucleotides in the neighbourhood of a (premature) termination codon","volume":"48","author":"Pacho","year":"2011","journal-title":"J. Med. Genet."},{"key":"2020031303072457700_ref43","doi-asserted-by":"crossref","first-page":"e1002608","DOI":"10.1371\/journal.pgen.1002608","article-title":"Statistical analysis of readthrough levels for nonsense mutations in mammalian cells reveals a major determinant of response to gentamicin","volume":"8","author":"Floquet","year":"2012","journal-title":"PLoS Genet."},{"key":"2020031303072457700_ref44","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1080\/15476286.2016.1219832","article-title":"Aminoglycoside-stimulated readthrough of premature termination codons in selected genes involved in primary ciliary dyskinesia","volume":"13","author":"Bukowy-Bieryllo","year":"2016","journal-title":"RNA Biol."},{"key":"2020031303072457700_ref45","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.pharmthera.2012.07.007","article-title":"Pharmaceutical therapies to recode nonsense mutations in inherited diseases","volume":"136","author":"Lee","year":"2012","journal-title":"Pharmacol. Ther."},{"key":"2020031303072457700_ref46","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nature05756","article-title":"PTC124 targets genetic disorders caused by nonsense mutations","volume":"447","author":"Welch","year":"2007","journal-title":"Nature"},{"key":"2020031303072457700_ref47","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1007\/s40265-014-0287-4","article-title":"Ataluren: first global approval","volume":"74","author":"Ryan","year":"2014","journal-title":"Drugs"},{"key":"2020031303072457700_ref48","doi-asserted-by":"crossref","first-page":"3332","DOI":"10.1523\/JNEUROSCI.3498-17.2019","article-title":"Genetic regulation of neuronal Progranulin reveals a critical role for the autophagy-lysosome pathway","volume":"39","author":"Elia","year":"2019","journal-title":"J. Neurosci."},{"key":"2020031303072457700_ref49","first-page":"969","article-title":"Progranulin regulates lysosomal function and biogenesis through acidification of lysosomes","volume":"26","author":"Tanaka","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"2020031303072457700_ref50","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s13024-018-0281-5","article-title":"Early lysosomal maturation deficits in microglia triggers enhanced lysosomal activity in other brain cells of progranulin knockout mice","volume":"13","author":"Gotzl","year":"2018","journal-title":"Mol. Neurodegener."},{"key":"2020031303072457700_ref51","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.ajhg.2012.04.021","article-title":"Strikingly different clinicopathological phenotypes determined by progranulin-mutation dosage","volume":"90","author":"Smith","year":"2012","journal-title":"Am. J. Hum. 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