{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:32:00Z","timestamp":1790188320240,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T00:00:00Z","timestamp":1601510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1144791"],"award-info":[{"award-number":["1144791"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Muscular Dystrophy Western Australia","award":["Postgraduate scholarship to D.L"],"award-info":[{"award-number":["Postgraduate scholarship to D.L"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parkin-type autosomal recessive juvenile-onset Parkinson\u2019s disease is caused by mutations in the PRKN gene and accounts for 50% of all autosomal recessive Parkinsonism cases. Parkin is a neuroprotective protein that has dual functions as an E3 ligase in the ubiquitin\u2013proteasome system and as a transcriptional repressor of p53. While genomic deletions of PRKN exon 3 disrupt the mRNA reading frame and result in the loss of functional parkin protein, deletions of both exon 3 and 4 maintain the reading frame and are associated with a later onset, milder disease progression, indicating this particular isoform retains some function. Here, we describe in vitro evaluation of antisense oligomers that restore functional parkin expression in cells derived from a Parkinson\u2019s patient carrying a heterozygous PRKN exon 3 deletion, by inducing exon 4 skipping to correct the reading frame. We show that the induced PRKN transcript is translated into a shorter but semi-functional parkin isoform able to be recruited to depolarised mitochondria, and also transcriptionally represses p53 expression. These results support the potential use of antisense oligomers as a disease-modifying treatment for selected pathogenic PRKN mutations.<\/jats:p>","DOI":"10.3390\/ijms21197282","type":"journal-article","created":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T20:18:28Z","timestamp":1601583508000},"page":"7282","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["A Splice Intervention Therapy for Autosomal Recessive Juvenile Parkinson\u2019s Disease Arising from Parkin Mutations"],"prefix":"10.3390","volume":"21","author":[{"given":"Dunhui","family":"Li","sequence":"first","affiliation":[{"name":"Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth 6150, Australia"},{"name":"Perron Institute for Neurological and Translational Science, University of Western Australia, Perth 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6379-2303","authenticated-orcid":false,"given":"May T.","family":"Aung-Htut","sequence":"additional","affiliation":[{"name":"Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth 6150, Australia"},{"name":"Perron Institute for Neurological and Translational Science, University of Western Australia, Perth 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7036-5334","authenticated-orcid":false,"given":"Kristin A.","family":"Ham","sequence":"additional","affiliation":[{"name":"Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth 6150, Australia"},{"name":"Perron Institute for Neurological and Translational Science, University of Western Australia, Perth 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8632-641X","authenticated-orcid":false,"given":"Sue","family":"Fletcher","sequence":"additional","affiliation":[{"name":"Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth 6150, Australia"},{"name":"Perron Institute for Neurological and Translational Science, University of Western Australia, Perth 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve D.","family":"Wilton","sequence":"additional","affiliation":[{"name":"Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth 6150, Australia"},{"name":"Perron Institute for Neurological and Translational Science, University of Western Australia, Perth 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/S1474-4422(06)70471-9","article-title":"Epidemiology of Parkinson\u2019s disease","volume":"5","author":"Breteler","year":"2006","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/00005072-199603000-00001","article-title":"Neuropathology of Parkinson\u2019s disease","volume":"55","author":"Forno","year":"1996","journal-title":"J. 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