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Cyclic adenosine monophosphate as an endogenous modulator of the amyloid-β precursor protein metabolism.
MedLine Citation:
PMID:  23297063     Owner:  NLM     Status:  Publisher    
Besides playing a pathogenic role in Alzheimer disease, amyloid-beta peptides are normally produced in low amounts in the brain, and several lines of evidence suggest that they can modulate synaptic plasticity and memory. As cyclic adenosine monophosphate (cAMP) is known to be involved in the same processes and the blockade of its degradation by phosphodiesterase 4 inhibitors has consistently shown beneficial effects on cognition, we investigated the possible correlation between this second messenger and Aβ peptides in neuronal N2a cells overexpressing the amyloid-β precursor protein (APP). We herein report that the elevation of endogenous cAMP by rolipram increased APP protein expression and both its amyloidogenic and nonamyloidogenic processing. The effects of rolipram were reproduced by both the cAMP membrane-permeant analog 8Br-cAMP and the forskolin-induced activation of adenylyl cyclase but were not affected by the PKA inhibitor H-89. Our results demonstrate that, in neuronal cells, APP metabolism is physiologically modulated by cAMP and suggest that this might represent an additional mechanism through which the second messenger could influence memory functions. © 2013 IUBMB Life, 2013.
Elisa Canepa; Cinzia Domenicotti; Barbara Marengo; Mario Passalacqua; Umberto M Marinari; Maria A Pronzato; Ernesto Fedele; Roberta Ricciarelli
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-8
Journal Detail:
Title:  IUBMB life     Volume:  -     ISSN:  1521-6551     ISO Abbreviation:  IUBMB Life     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888706     Medline TA:  IUBMB Life     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.
Department of Experimental Medicine, University of Genoa, Genoa, Italy.
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