English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/170598
COMPARTIR / IMPACTO:
Estadísticas
logo share SHARE   Add this article to your Mendeley library MendeleyBASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Título

Pantothenate Rescues Iron Accumulation in Pantothenate Kinase-Associated Neurodegeneration Depending on the Type of Mutation

AutorÁlvarez-Córdoba, Mónica; Fernández-Khoury, Aida; Villanueva Paz, Marina; Gómez-Navarro, Carmen; Villalón-García, Irene; Suarez-Rivero, Juan M.; Povea-Cabello, Suleva; Mata, Mario de la ; Cotán, David ; Talaverón-Rey, Marta; Salas, Joaquín J. ; Pérez-Villegas, Eva Mª; Díaz-Quintana, Antonio; Armengol, José A.; Sánchez-Alcázar, José Antonio
Palabras clavePantothenate kinase
Coenzyme A
Mitochondria
Pantothenate
Induced neurons
Fecha de publicación1-sep-2018
EditorSpringer
CitaciónMolecular Neurobiology (2018)
ResumenNeurodegeneration with brain iron accumulation (NBIA) is a group of inherited neurologic disorders in which iron accumulates in the basal ganglia resulting in progressive dystonia, spasticity, parkinsonism, neuropsychiatric abnormalities, and optic atrophy or retinal degeneration. The most prevalent form of NBIA is pantothenate kinase-associated neurodegeneration (PKAN) associated with mutations in the gene of pantothenate kinase 2 (PANK2), which is essential for coenzyme A (CoA) synthesis. There is no cure for NBIA nor is there a standard course of treatment. In the current work, we describe that fibroblasts derived from patients harbouring PANK2 mutations can reproduce many of the cellular pathological alterations found in the disease, such as intracellular iron and lipofuscin accumulation, increased oxidative stress, and mitochondrial dysfunction. Furthermore, mutant fibroblasts showed a characteristic senescent morphology. Treatment with pantothenate, the PANK2 enzyme substrate, was able to correct all pathological alterations in responder mutant fibroblasts with residual PANK2 enzyme expression. However, pantothenate had no effect on mutant fibroblasts with truncated/incomplete protein expression. The positive effect of pantothenate in particular mutations was also confirmed in induced neurons obtained by direct reprograming of mutant fibroblasts. Our results suggest that pantothenate treatment can stabilize the expression levels of PANK2 in selected mutations. These results encourage us to propose our screening model as a quick and easy way to detect pantothenate-responder patients with PANK2 mutations. The existence of residual enzyme expression in some affected individuals raises the possibility of treatment using high dose of pantothenate.
Descripción50 Páginas; 9 Figuras
Versión del editorhttp://dx.doi.org/10.1007/s12035-018-1333-0
URIhttp://hdl.handle.net/10261/170598
ISSN0893-7648
E-ISSN1559-1182
Aparece en las colecciones: (IG) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
Postprint_2018_Mol_Neurobiol_Pantothenate.pdf Embargado hasta 1 de septiembre de 2019Artículo principal7,03 MBAdobe PDFVista previa
Visualizar/Abrir     Petición de una copia
Mostrar el registro completo
 


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.