Álvarez-Córdoba, M.; Talaverón-Rey, M.; Povea-Cabello, S.; Cilleros-Holgado, P.; Gómez-Fernández, D.; Piñero-Pérez, R.; Reche-López, D.; Munuera-Cabeza, M.; Suárez-Carrillo, A.; Romero-González, A.; Romero-Domínguez, J.M.; López-Cabrera, A.; Armengol, J.Á.; Sánchez-Alcázar, J.A. Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration. Pharmaceuticals2023, 16, 1359.
Álvarez-Córdoba, M.; Talaverón-Rey, M.; Povea-Cabello, S.; Cilleros-Holgado, P.; Gómez-Fernández, D.; Piñero-Pérez, R.; Reche-López, D.; Munuera-Cabeza, M.; Suárez-Carrillo, A.; Romero-González, A.; Romero-Domínguez, J.M.; López-Cabrera, A.; Armengol, J.Á.; Sánchez-Alcázar, J.A. Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration. Pharmaceuticals 2023, 16, 1359.
Álvarez-Córdoba, M.; Talaverón-Rey, M.; Povea-Cabello, S.; Cilleros-Holgado, P.; Gómez-Fernández, D.; Piñero-Pérez, R.; Reche-López, D.; Munuera-Cabeza, M.; Suárez-Carrillo, A.; Romero-González, A.; Romero-Domínguez, J.M.; López-Cabrera, A.; Armengol, J.Á.; Sánchez-Alcázar, J.A. Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration. Pharmaceuticals2023, 16, 1359.
Álvarez-Córdoba, M.; Talaverón-Rey, M.; Povea-Cabello, S.; Cilleros-Holgado, P.; Gómez-Fernández, D.; Piñero-Pérez, R.; Reche-López, D.; Munuera-Cabeza, M.; Suárez-Carrillo, A.; Romero-González, A.; Romero-Domínguez, J.M.; López-Cabrera, A.; Armengol, J.Á.; Sánchez-Alcázar, J.A. Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration. Pharmaceuticals 2023, 16, 1359.
Abstract
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). Nowadays, 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 commercial pharmacological or natural compounds for implementing polytarget precision medicine in PKAN. In the last years, several studies have described that PKAN patient-derived fibroblasts manifest the main pathological changes associated with the disease including intracellular iron overload. Interestingly, treatment of mutant cell cultures with various supplements such as pantothenate, pantethine, thiamine, L-carnitine, vitamin E, omega 3, and -lipoic acid 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 to optimize therapeutic strategies in individual PKAN patients.
Keywords
neurodegeneration with brain iron accumulation (NBIA); pantothenate kinaseassociated neurodegeneration (PKAN); pantothenate kinase 2 (PANK2); pantothenate; pantethine; vitamin E; omega 3; -lipoic acid; L-carnitine; thiamine; fibroblasts; induced neurons; precision medicine
Subject
Biology and Life Sciences, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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