期刊
NEUROSCIENCE
卷 161, 期 4, 页码 978-987出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2009.04.002
关键词
cleaved caspase-3; Alzheimer's disease; apoptosis; Tet-off; hippocampal neurons; neuro-2a cell line
资金
- Fondecyt [3010060, 1060040]
- Initiative Scientific Millennium [ICMP05-001-F]
- International Center for Biomedicine
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 (GSK3 beta), 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 hyper-phosphorylation 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 annyloid beta 1-42 (A beta(1-42)) 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 A beta treatment in the apoptosis of neuronal cells. These results represent a linkage between amyloidogenic and cdk5 pathways leading to apoptosis of neuronal cells. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.
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