CYCLIN-DEPENDENT KINASE 5 ACTIVATOR p35 OVER-EXPRESSION AND AMYLOID BETA SYNERGISM INCREASE APOPTOSIS IN CULTURED NEURONAL CELLS

Utreras, E; Maccioni, R; Gonzalez-Billault, C

Abstract

Alzheimer disease (AD) is a neurodegenerative disorder characterized by neuronal loss, dementia and pain. Two main protein aggregates, extracellular (senile plaques, SP) and intracellular (neurofibrillary tangles, NFT), are associated with AD. NFT are mainly composed of hyperphosphorylated microtubule-associated protein tau. Nowadays several protein kinases have been implicated in the phosphorylation of tau, including glycogen synthase kinase 3 beta (GSK3ß), MAP kinase, protein kinase A and cyclin-dependent kinase 5 (Cdk5). A deregulation in the activity of Cdk5 has been postulated to participate in the abnormal tau hyperphosphorylation in AD. Activation of Cdk5 occurs after its association with p35, a neuron-specific activator, predominantly in the nervous system. Therefore, in this study we used the tetracycline transactivator system to increase p35/GFP in neuronal cells, treated with amyloid beta 1-42 (Aß1-42) peptide. These cells showed an increase of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and cleaved caspase-3 staining, indicating increased apoptosis of neuronal cells. This effect could be reversed by the addition of tetracycline in the culture medium, suggesting synergistic effects of p35 over-expression and Aß treatment in the apoptosis of neuronal cells. These results represent a linkage between amyloidogenic and cdk5 pathways leading to apoptosis of neuronal cells. © 2009 IBRO.

Más información

Título según WOS: CYCLIN-DEPENDENT KINASE 5 ACTIVATOR p35 OVER-EXPRESSION AND AMYLOID BETA SYNERGISM INCREASE APOPTOSIS IN CULTURED NEURONAL CELLS
Título según SCOPUS: Cyclin-dependent kinase 5 activator p35 over-expression and amyloid beta synergism increase apoptosis in cultured neuronal cells
Título de la Revista: NEUROSCIENCE
Volumen: 161
Número: 4
Editorial: Elsevier
Fecha de publicación: 2009
Página de inicio: 978
Página final: 987
Idioma: English
URL: http://linkinghub.elsevier.com/retrieve/pii/S030645220900582X
DOI:

10.1016/j.neuroscience.2009.04.002

Notas: ISI, SCOPUS