Inhibition of CDKs: a strategy for preventing kainic acid-induced apoptosis in neurons.
Stimulation of ionotropic glutamate receptors are implicated in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Recently this has been demonstrated in the expression of cell cycle proteins in vulnerable neurons in Alzheimer's disease. Thus, the aim of the present study was to evaluate the expression of cell cycle proteins in cerebellar granule cells after stimulation of AMPA/KA receptors and likewise to study the neuroprotective effects of CDK inhibitors. Our results demonstrated that after a treatment with CDK inhibitors, a significant decrease in apoptotic nuclei induced by kainic acid was found in the presence of flavopiridol and 3-ATA. We concluded that CDK activation is involved, at least, in part, in the pro-apoptotic effects of kainic acid.
Verdaguer
E
E
Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain. verdague@farmacia.far.ub.es
Jordà
Elvira G
EG
Stranges
Alessandra
A
Canudas
Anna M
AM
Jiménez
Andrés
A
Sureda
Francesc X
FX
Pallas
Mercè
M
Camins
Antoni
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D007608:Kainic Acid / Q000633:toxicity*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats
D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D010880:Piperidines; C077990:alvocidib; D018844:Cyclin-Dependent Kinases; D007608:Kainic Acid