Cyclic adenosine monophosphate (cAMP) modulates synaptic plasticity and memory and manipulation of the cAMP/protein kinase A/cAMP responsive element binding protein pathway significantly affects cognitive functions. Notably, cAMP can increase the expression of the amyloid precursor protein (APP), whose proteolytic processing gives rise to amyloid beta (Aβ) peptides. Despite playing a pathogenic role in Alzheimer's disease, physiological concentrations of Aβ are necessary for the cAMP-mediated regulation of long-term potentiation, supporting the existence of a novel cAMP/APP/Aβ cascade with a crucial role in memory formation. However, the molecular mechanisms by which cAMP stimulates APP expression and Aβ production remain unclear. Here, we investigated whether hnRNP-C and FMRP, two RNA-binding proteins largely involved in the expression of APP, are the cAMP effectors inducing the protein synthesis of APP. Using RNA immunoprecipitation and RNA-silencing approaches, we found that neither hnRNP-C nor FMRP is required for cAMP to stimulate APP and Aβ production.
Keywords: Alzheimer's disease; RNA-bindin protein; amyloid beta; amyloid precursor protein; forskolin.
© 2015 International Union of Biochemistry and Molecular Biology.