cAMP delays beta-amyloid (25-35) induced cell death in rat cortical neurons.
Beta-amyloid (A beta) accumulation is believed to contribute to neuronal cell death in Alzheimer's disease. To understand the role of cAMP in the regulation of A beta induced cell death, we used 8-chlorophenylthio-cAMP (8-CPT-cAMP, a cAMP analog) to raise intracellular cAMP levels. Exposure of rat cortical neurons to A beta(25-35) resulted in a gradual increase in lactate dehydrogenase (LDH) over 48 h, which was preceded by a transient elevation in caspase-3-like activity. In the presence of 8CPT-cAMP, both caspase-3 activity and LDH release was significantly reduced. These data suggest that elevation of intracellular cAMP levels attenuate A beta-induced neurotoxicity and may delay or prevent the onset of A beta-induced neurodegeneration.
GU/Neuroscience Drug Discovery, Pharmaceutical Research Institute, Bristol-Myers Squibb, Wallingford, CT 06492, USA.
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Calandra
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D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000502:physiology; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000502:physiology*; D004622:Embryo, Mammalian; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013873:Thionucleotides / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D009498:Neurotoxins; D010446:Peptide Fragments; D013873:Thionucleotides; C074636:amyloid beta-protein (25-35); C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D000242:Cyclic AMP; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases