{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T21:25:07Z","timestamp":1772832307692,"version":"3.50.1"},"reference-count":207,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T00:00:00Z","timestamp":1695686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III","award":["PI19\/00377"],"award-info":[{"award-number":["PI19\/00377"]}]},{"name":"Instituto de Salud Carlos III","award":["PI22\/00142"],"award-info":[{"award-number":["PI22\/00142"]}]},{"name":"Instituto de Salud Carlos III","award":["PY18-850"],"award-info":[{"award-number":["PY18-850"]}]},{"name":"Instituto de Salud Carlos III","award":["UPO-FEDER 2018 (UPO-1380614)"],"award-info":[{"award-number":["UPO-FEDER 2018 (UPO-1380614)"]}]},{"name":"Fondo Europeo de Desarrollo Regional (FEDER-Uni\u00f3n Europea)","award":["PI19\/00377"],"award-info":[{"award-number":["PI19\/00377"]}]},{"name":"Fondo Europeo de Desarrollo Regional (FEDER-Uni\u00f3n Europea)","award":["PI22\/00142"],"award-info":[{"award-number":["PI22\/00142"]}]},{"name":"Fondo Europeo de Desarrollo Regional (FEDER-Uni\u00f3n Europea)","award":["PY18-850"],"award-info":[{"award-number":["PY18-850"]}]},{"name":"Fondo Europeo de Desarrollo Regional (FEDER-Uni\u00f3n Europea)","award":["UPO-FEDER 2018 (UPO-1380614)"],"award-info":[{"award-number":["UPO-FEDER 2018 (UPO-1380614)"]}]},{"name":"Proyectos de Investigaci\u00f3n de Excelencia de la Junta de Andaluc\u00eda","award":["PI19\/00377"],"award-info":[{"award-number":["PI19\/00377"]}]},{"name":"Proyectos de Investigaci\u00f3n de Excelencia de la Junta de Andaluc\u00eda","award":["PI22\/00142"],"award-info":[{"award-number":["PI22\/00142"]}]},{"name":"Proyectos de Investigaci\u00f3n de Excelencia de la Junta de Andaluc\u00eda","award":["PY18-850"],"award-info":[{"award-number":["PY18-850"]}]},{"name":"Proyectos de Investigaci\u00f3n de Excelencia de la Junta de Andaluc\u00eda","award":["UPO-FEDER 2018 (UPO-1380614)"],"award-info":[{"award-number":["UPO-FEDER 2018 (UPO-1380614)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The term neurodegeneration with brain iron accumulation (NBIA) brings together a broad set of progressive and disabling neurological genetic disorders in which iron is deposited preferentially in certain areas of the brain. Among NBIA disorders, the most frequent subtype is pantothenate kinase-associated neurodegeneration (PKAN) caused by pathologic variants in the PANK2 gene codifying the enzyme pantothenate kinase 2 (PANK2). To date, there are no effective treatments to stop the progression of these diseases. This review discusses the utility of patient-derived cell models as a valuable tool for the identification of pharmacological or natural compounds for implementing polytarget precision medicine in PKAN. Recently, several studies have described that PKAN patient-derived fibroblasts present the main pathological features associated with the disease including intracellular iron overload. Interestingly, treatment of mutant cell cultures with various supplements such as pantothenate, pantethine, vitamin E, omega 3, \u03b1-lipoic acid L-carnitine or thiamine, improved all pathophysiological alterations in PKAN fibroblasts with residual expression of the PANK2 enzyme. The information provided by pharmacological screenings in patient-derived cellular models can help optimize therapeutic strategies in individual PKAN patients.<\/jats:p>","DOI":"10.3390\/ph16101359","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T08:55:01Z","timestamp":1695718501000},"page":"1359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration"],"prefix":"10.3390","volume":"16","author":[{"given":"M\u00f3nica","family":"\u00c1lvarez-C\u00f3rdoba","sequence":"first","affiliation":[{"name":"Andalusian Centre for Developmental Biology (CABD-CSIC-Pablo de Olavide University), 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Talaver\u00f3n-Rey","sequence":"additional","affiliation":[{"name":"Andalusian Centre for Developmental Biology (CABD-CSIC-Pablo de Olavide University), 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suleva","family":"Povea-Cabello","sequence":"additional","affiliation":[{"name":"Andalusian Centre for Developmental Biology (CABD-CSIC-Pablo de Olavide University), 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Cilleros-Holgado","sequence":"additional","affiliation":[{"name":"Andalusian Centre for Developmental Biology (CABD-CSIC-Pablo de Olavide University), 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"G\u00f3mez-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Andalusian Centre for Developmental Biology (CABD-CSIC-Pablo de Olavide University), 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roc\u00edo","family":"Pi\u00f1ero-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Andalusian Centre for Developmental Biology (CABD-CSIC-Pablo de Olavide University), 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Reche-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Andalusian Centre for Developmental Biology (CABD-CSIC-Pablo de Olavide University), 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Munuera-Cabeza","sequence":"additional","affiliation":[{"name":"Andalusian Centre for Developmental Biology (CABD-CSIC-Pablo de Olavide University), 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandra","family":"Su\u00e1rez-Carrillo","sequence":"additional","affiliation":[{"name":"Andalusian Centre for Developmental Biology (CABD-CSIC-Pablo de Olavide University), 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Romero-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Andalusian Centre for Developmental Biology (CABD-CSIC-Pablo de Olavide University), 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose Manuel","family":"Romero-Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Andalusian Centre for Developmental Biology (CABD-CSIC-Pablo de Olavide University), 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandra","family":"L\u00f3pez-Cabrera","sequence":"additional","affiliation":[{"name":"Andalusian Centre for Developmental Biology (CABD-CSIC-Pablo de Olavide University), 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9452-7828","authenticated-orcid":false,"given":"Jos\u00e9 \u00c1ngel","family":"Armengol","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Cellular Biology, Pablo de Olavide University, 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9705-1469","authenticated-orcid":false,"given":"Jos\u00e9 Antonio","family":"S\u00e1nchez-Alc\u00e1zar","sequence":"additional","affiliation":[{"name":"Andalusian Centre for Developmental Biology (CABD-CSIC-Pablo de Olavide University), 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.ymgme.2016.11.004","article-title":"Consensus clinical management guideline for pantothenate kinase-associated neurodegeneration (PKAN)","volume":"120","author":"Hogarth","year":"2017","journal-title":"Mol. 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