Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration

Álvarez-Córdoba, Mónica; Talaverón-Rey, Marta; Povea-Cabello, Suleva; Cilleros-Holgado, Paula; Gómez-Fernández, David; Piñero-Perez, Rocío; Reche-López, Diana; Munuera, Manuel; Suárez-Carrillo, Alejandra; Romero-González, Ana; Romero-Domínguez, José Manuel; López-Cabrera, Alejandra; Armengol, José Ángel; Sánchez-Alcázar, José Antonio

Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration

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-assoc...

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Autores:	Álvarez-Córdoba, Mónica, Talaverón-Rey, Marta, Povea-Cabello, Suleva, Cilleros-Holgado, Paula, Gómez-Fernández, David, Piñero-Perez, Rocío, Reche-López, Diana, Munuera, Manuel, Suárez-Carrillo, Alejandra, Romero-González, Ana, Romero-Domínguez, José Manuel, López-Cabrera, Alejandra, Armengol, José Ángel, Sánchez-Alcázar, José Antonio
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2023
País:	España
Institución:	Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:	DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:	oai:digital.csic.es:10261/341877
Acceso en línea:	http://hdl.handle.net/10261/341877
Access Level:	acceso abierto
Palabra clave:	Neurodegeneration with brain iron accumulation (NBIA) Pantothenate kinase-associated neurodegeneration (PKAN) Pantothenate kinase 2 (PANK2) Pantothenate Pantethine Vitamin E Omega 3 α-lipoic acid L-carnitine Thiamine Fibroblasts Induced neurons Precision medicine

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spelling	Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated NeurodegenerationÁlvarez-Córdoba, MónicaTalaverón-Rey, MartaPovea-Cabello, SulevaCilleros-Holgado, PaulaGómez-Fernández, DavidPiñero-Perez, RocíoReche-López, DianaMunuera, ManuelSuárez-Carrillo, AlejandraRomero-González, AnaRomero-Domínguez, José ManuelLópez-Cabrera, AlejandraArmengol, José ÁngelSánchez-Alcázar, José AntonioNeurodegeneration with brain iron accumulation (NBIA)Pantothenate kinase-associated neurodegeneration (PKAN)Pantothenate kinase 2 (PANK2)PantothenatePantethineVitamin EOmega 3α-lipoic acidL-carnitineThiamineFibroblastsInduced neuronsPrecision medicineThe 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, α-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.This work was supported by PI19/00377 and PI22/00142 grants, Instituto de Salud Carlos III, Spain and Fondo Europeo de Desarrollo Regional (FEDER-Unión Europea), Proyectos de Investigación de Excelencia de la Junta de Andalucía PY18-850 and UPO-FEDER 2018 (UPO-1380614).Peer reviewedMultidisciplinary Digital Publishing InstituteInstituto de Salud Carlos IIIEuropean CommissionJunta de AndalucíaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2024202420232024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_dcae04bcPublisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/341877reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.3390/ph16101359Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3418772026-05-22T06:33:51Z
dc.title.none.fl_str_mv	Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration
title	Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration
spellingShingle	Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration Álvarez-Córdoba, Mónica Neurodegeneration with brain iron accumulation (NBIA) Pantothenate kinase-associated neurodegeneration (PKAN) Pantothenate kinase 2 (PANK2) Pantothenate Pantethine Vitamin E Omega 3 α-lipoic acid L-carnitine Thiamine Fibroblasts Induced neurons Precision medicine
title_short	Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration
title_full	Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration
title_fullStr	Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration
title_full_unstemmed	Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration
title_sort	Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration
dc.creator.none.fl_str_mv	Álvarez-Córdoba, Mónica Talaverón-Rey, Marta Povea-Cabello, Suleva Cilleros-Holgado, Paula Gómez-Fernández, David Piñero-Perez, Rocío Reche-López, Diana Munuera, Manuel Suárez-Carrillo, Alejandra Romero-González, Ana Romero-Domínguez, José Manuel López-Cabrera, Alejandra Armengol, José Ángel Sánchez-Alcázar, José Antonio
author	Álvarez-Córdoba, Mónica
author_facet	Álvarez-Córdoba, Mónica Talaverón-Rey, Marta Povea-Cabello, Suleva Cilleros-Holgado, Paula Gómez-Fernández, David Piñero-Perez, Rocío Reche-López, Diana Munuera, Manuel Suárez-Carrillo, Alejandra Romero-González, Ana Romero-Domínguez, José Manuel López-Cabrera, Alejandra Armengol, José Ángel Sánchez-Alcázar, José Antonio
author_role	author
author2	Talaverón-Rey, Marta Povea-Cabello, Suleva Cilleros-Holgado, Paula Gómez-Fernández, David Piñero-Perez, Rocío Reche-López, Diana Munuera, Manuel Suárez-Carrillo, Alejandra Romero-González, Ana Romero-Domínguez, José Manuel López-Cabrera, Alejandra Armengol, José Ángel Sánchez-Alcázar, José Antonio
author2_role	author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Instituto de Salud Carlos III European Commission Junta de Andalucía Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv	Neurodegeneration with brain iron accumulation (NBIA) Pantothenate kinase-associated neurodegeneration (PKAN) Pantothenate kinase 2 (PANK2) Pantothenate Pantethine Vitamin E Omega 3 α-lipoic acid L-carnitine Thiamine Fibroblasts Induced neurons Precision medicine
topic	Neurodegeneration with brain iron accumulation (NBIA) Pantothenate kinase-associated neurodegeneration (PKAN) Pantothenate kinase 2 (PANK2) Pantothenate Pantethine Vitamin E Omega 3 α-lipoic acid L-carnitine Thiamine Fibroblasts Induced neurons Precision medicine
description	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, α-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.
publishDate	2023
dc.date.none.fl_str_mv	2023 2024 2024 2024
dc.type.none.fl_str_mv	info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_dcae04bc Publisher's version info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	http://hdl.handle.net/10261/341877
url	http://hdl.handle.net/10261/341877
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	http://dx.doi.org/10.3390/ph16101359 Sí
dc.rights.none.fl_str_mv	info:eu-repo/semantics/openAccess
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv	Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv	reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str	Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str	DIGITAL.CSIC. Repositorio Institucional del CSIC
collection	DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15,811543

Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration

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