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Title

Simvastatin overcomes the resistance to serum withdrawal-induced apoptosis of lymphocytes from Alzheimer´s disease patients

AuthorsBartolomé Robledo, Fernando ; Muñoz, Úrsula ; Esteras, Noemí ; Alquézar, Carolina ; Collado, Andrea; Bermejo-Pareja, Félix; Martín-Requero, Ángeles
KeywordsAlzheimer’s disease
Lymphocytes
Simvastatin
p21
PI3K/Akt
ERK1/2
Issue Date8-Jul-2010
PublisherSpringer
CitationCellular and Molecular Life Sciences 67(24):4257-4268(2010)
AbstractStatins may exert beneficial effects on Alzheimer’s disease (AD) patients. Based on the antineoplastic and apoptotic effects of statins in a number of cell types, we hypothesized that statins may be able to protect neurons by controlling the regulation of cell cycle and/or apoptosis. A growing body of evidence indicates that neurodegeneration involves the cell-cycle activation in postmitotic neurons. Failure of cell-cycle control is not restricted to neurons in AD patients, but occurs in peripheral cells as well. For these reasons, we studied the role of simvastatin (SIM) on cell survival/death in lymphoblasts from AD patients. We report here that SIM induces apoptosis in AD lymphoblasts deprived of serum. SIM interacts with PI3K/Akt and ERK1/2 signaling pathways thereby decreasing the serum withdrawal-enhanced levels of the CDK inhibitor p21Cip1 (p21) and restoring the vulnerability of AD cells to trophic factor deprivation
Description12 páginas, 9 figuras, 1 tabla -- PAGS nros. 4268-4257
Publisher version (URL)http://dx.doi.org/10.1007/s00018-010-0443-2
URIhttp://hdl.handle.net/10261/52414
DOI10.1007/s00018-010-0443-2
ISSN1420-682X
E-ISSN1420-9071
Appears in Collections:(CIB) Artículos
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