cAMP delays beta-amyloid (25-35) induced cell death in rat cortical neurons.

Neuroreport

GU/Neuroscience Drug Discovery, Pharmaceutical Research Institute, Bristol-Myers Squibb, Wallingford, CT 06492, USA.

Published: July 2000

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.

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http://dx.doi.org/10.1097/00001756-200007140-00045DOI Listing

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