A cdk5-p35 stable complex is involved in the beta-amyloid-induced deregulation of cdk5 activity in hippocampal neurons
Abstract
The cdk5 and its activator p35 constitute one of the main tau-phosphorylating systems in neuronal cells. Under normal conditions for neurons, its activity is required for modulating tau involvement in neuronal polarity and in development of the mammalian central nervous system. Recently, we reported that the treatment of rat hippocampal cells in culture with fibrillary ?-amyloid (A?) results in deregulation of the protein kinase cdk5. The neurotoxic effects of A? fibrils were prevented by inhibition of cdk5 activity by butyrolactone I or by using antisense oligonucleotides that control the expression of this kinase. Here, we show that the A?-promoted increase of cdk5 activity is associated with changes in tau phosphorylation patterns and in the intraneuronal distribution of tau. In addition to hippocampal cells, deregulation of cdk5 was observed in other cell types. However, butyrolactone I prevented A?-induced cell death only in neuronal cells in which cdk5 activation was sensitive to A? fibrils. This lost of cdk5 regulation in hippocampal cells exposed to A? fibrils appears to be associated with an increase in the cdk5-p35 complex stability. Complex stabilization was sensitive to phosphorylation of cdk5. However, no changes in cdk5 and p35 mRNAs were observed, suggesting that the main effects on cdk5 occur at the posttranslational level. These studies indicate that cdk5 phosphorylation and the formation of an abnormally active cdk5-p35 complex are directly involved in the molecular paths leading to the neurodegenerative process of rat hippocampal neurons triggered by A? fibrils. © 2001 Academic Press.
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Título según WOS: | A cdk5-p35 stable complex is involved in the beta-amyloid-induced deregulation of cdk5 activity in hippocampal neurons |
Título según SCOPUS: | A cdk5-p35 stable complex is involved in the ?-amyloid-induced deregulation of cdk5 activity in hippocampal neurons |
Título de la Revista: | EXPERIMENTAL CELL RESEARCH |
Volumen: | 264 |
Número: | 2 |
Editorial: | ELSEVIER INC |
Fecha de publicación: | 2001 |
Página de inicio: | 266 |
Página final: | 274 |
Idioma: | English |
URL: | http://linkinghub.elsevier.com/retrieve/pii/S0014482701951523 |
DOI: |
10.1006/excr.2001.5152 |
Notas: | ISI, SCOPUS |