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To identify a new pathway that might be responsible for such impairment, we analyzed the role of the nitric oxide (NO)\/soluble guanylyl cyclase (sGC)\/cGMP\/cGMP-dependent protein kinase (cGK)\/cAMP-responsive element-binding protein (CREB) cascade because of its involvement in LTP. The use of the NO donor 2-(<jats:italic>N<\/jats:italic>,<jats:italic>N<\/jats:italic>-dethylamino)-diazenolate-2-oxide diethylammonium salt (DEA\/NO), the sGC stimulator 3-(4-amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1<jats:italic>H<\/jats:italic>-pyrazolo[3,4-b]pyridine, or the cGMP-analogs 8-bromo-cGMP and 8-(4-chlorophenylthio)-cGMP reversed the A\u03b2-induced impairment of CA1-LTP through cGK activation. Furthermore, these compounds reestablished the enhancement of CREB phosphorylation occurring during LTP in slices exposed to A\u03b2. We also found that A\u03b2 blocks the increase in cGMP immunoreactivity occurring immediately after LTP and that DEA\/NO counteracts the effect of A\u03b2. These results strongly suggest that, when modulating hippocampal synaptic plasticity, A\u03b2 downregulates the NO\/cGMP\/cGK\/CREB pathway; thus, enhancement of the NO\/cGMP signaling may provide a novel approach to the treatment of AD and other neurodegenerative diseases with elevated production of A\u03b2.<\/jats:p>","DOI":"10.1523\/jneurosci.5291-04.2005","type":"journal-article","created":{"date-parts":[[2005,7,20]],"date-time":"2005-07-20T16:26:06Z","timestamp":1121876766000},"page":"6887-6897","source":"Crossref","is-referenced-by-count":209,"title":["Amyloid-\u03b2 Peptide Inhibits Activation of the Nitric Oxide\/cGMP\/cAMP-Responsive Element-Binding Protein Pathway during Hippocampal Synaptic 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