Simvastatin overcomes the resistance to serum withdrawal-induced apoptosis of lymphocytes from Alzheimer's disease patients.
Statins 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 p21(Cip1) (p21) and restoring the vulnerability of AD cells to trophic factor deprivation.
Bartolomé
Fernando
F
Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas (CSIC), Ramiro de Maeztu 9, 28040, Madrid, Spain.
Muñoz
Ursula
U
Esteras
Noemí
N
Alquezar
Carolina
C
Collado
Andrea
A
Bermejo-Pareja
Félix
F
Martín-Requero
Angeles
A
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D047428:Protein Kinase Inhibitors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D044967:Serum / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D019821:Simvastatin / Q000494:pharmacology*
D050759:Cyclin-Dependent Kinase Inhibitor p21; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D047428:Protein Kinase Inhibitors; D019821:Simvastatin; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases