Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/61073
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Alterations in cell cycle-related proteins in lymphoblasts from carries of the c.709-1G>A PGRN mutation associated with FTLD-TDP dementia |
Autor: | Alquézar, Carolina CSIC ORCID; Esteras, Noemí CSIC ORCID; Bartolomé Robledo, Fernando CSIC ORCID; Merino, José J.; Alzualde, Ainhoa; López de Munain, Adolfo; Martín-Requero, Ángeles CSIC ORCID | Palabras clave: | FTLD Lymphocytes Cell cycle pRb CDK6 TDP-43 |
Fecha de publicación: | feb-2012 | Editor: | Elsevier | Citación: | Neurobiology of Aging 33(2):429.e7-429.e20(2012) | Resumen: | Frontotemporal lobar degeneration with neuronal inclusions containing TAR DNA binding protein 43 (TDP-43) is associated in most cases with null-mutations in the progranulin gene (PGRN). While the mechanisms by which PGRN haploinsufficiency leads to neurodegeneration remained speculative, increasing evidence support the hypothesis that cell cycle reentry of postmitotic neurons precedes many instances of neuronal death. Based in the mitogenic and neurotrophic activities of PGRN, we hypothesized that PGRN deficit may induce cell cycle disturbances and alterations in neuronal vulnerability. Because cell cycle dysfunction is not restricted to neurons, we studied the influence of PGRN haploinsufficiency, on cell cycle control in peripheral cells from patients suffering from frontotemporal dementia, bearing the PGRN mutation c.709-1G>A. Here we show that progranulin deficit increased cell cycle activity in immortalized lymphocytes. This effect was associated with increased levels of cyclin-dependent kinase 6 (CDK6) and phosphorylation of retinoblastoma protein (pRb), resulting in a G1/S regulatory failure. A loss of function of TDP-43 repressing CDK6 expression may result from altered subcellular TDP-43 distribution. The distinct functional features of lymphoblastoid cells from c.709-1 G>A carriers offer an invaluable, noninvasive tool to investigate the etiopathogenesis of frontotemporal lobar degeneration | Descripción: | 429.e7–429.e20 páginas, 8 figuras, 1 tabla | Versión del editor: | http://dx.doi.org/10.1016/j.neurobiolaging.2010.11.020 | URI: | http://hdl.handle.net/10261/61073 | DOI: | 10.1016/j.neurobiolaging.2010.11.020 | ISSN: | 0197-4580 | E-ISSN: | 1558-1497 |
Aparece en las colecciones: | (CIB) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
Alquezar_NBA_2012_33_2.pdf | 570,85 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
SCOPUSTM
Citations
20
checked on 17-abr-2024
WEB OF SCIENCETM
Citations
20
checked on 28-feb-2024
Page view(s)
458
checked on 24-abr-2024
Download(s)
304
checked on 24-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.