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Título: | G1/S cell cycle checkpoint dysfunction in lymphoblasts from sporadic Parkinson’s disease patients. |
Autor: | Esteras, Noemí CSIC ORCID; Alquézar, Carolina CSIC ORCID; Bartolomé Robledo, Fernando CSIC ORCID; De la Encarnación, Ana CSIC ORCID; Bermejo-Pareja, Félix; Molina, J.A.; Martín-Requero, Ángeles CSIC ORCID | Palabras clave: | Parkinson disease Lymphocytes Cell cycle pRb CDK6 TDP-43 Cyclin D3 Rapamycin Sodium butyrate PD-332991 |
Fecha de publicación: | 3-sep-2014 | Editor: | Humana Press | Citación: | Molecular Neurobiology, 2014 | Resumen: | Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease among aging individuals, affecting greatly the quality of their life. However, the pathogenesis of Parkinson's disease is still incompletely understood to date. Increasing experimental evidence suggests that cell cycle reentry of postmitotic neurons precedes many instances of neuronal death. Since cell cycle dysfunction is not restricted to neurons, we investigated this issue in peripheral cells from patients suffering from sporadic PD and age-matched control individuals. Here, we describe increased cell cycle activity in immortalized lymphocytes from PD patients, that is associated to enhanced activity of the cyclin D3/CDK6 complex, resulting in higher phosphorylation of the pRb family protein and thus, in a G1/S regulatory failure. Decreased degradation of cyclin D3, together with increased p21 degradation, as well as elevated levels of CDK6 mRNA and protein were found in PD lymphoblasts. Inhibitors of cyclin D3/CDK6 activity like sodium butyrate, PD-332991, and rapamycin were able to restore the response of PD cells to serum stimulation. We conclude that lymphoblasts from PD patients are a suitable model to investigate cell biochemical aspects of this disease. It is suggested that cyclin D3/CDK6-associated kinase activity could be potentially a novel therapeutic target for the treatment of PD. | Descripción: | 38 p.-8 fig. | Versión del editor: | http://dx.doi.org/10.1007/s12035-014-8870-y | URI: | http://hdl.handle.net/10261/108791 | DOI: | 10.1007/s12035-014-8870-y | ISSN: | 0893-7648 | E-ISSN: | 1559-1182 |
Aparece en las colecciones: | (CIB) Artículos |
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MOLN 2014, Martín-Requero.pdf | 2 MB | Adobe PDF | Visualizar/Abrir |
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