title: Evaluating the role of hnRNP-C and FMRP in the cAMP-induced APP metabolism.
abstract: 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.
authors: Department of Experimental Medicine, University of Genoa, Genoa, Italy.
authors: D
authors: D
authors: Rivera
authors: E
authors: E
authors: Fedele
authors: U M
authors: UM
authors: Marinari
authors: M A
authors: MA
authors: Pronzato
authors: R
authors: R
authors: Ricciarelli
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D016564:Amyloid beta-Protein Precursor; D005576:Colforsin; D000242:Cyclic AMP; D051860:Fragile X Messenger Ribonucleoprotein 1; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C; D034741:RNA, Small Interfering; C497684:Fmr1 protein, mouse; C503633:Hnrnpc protein, mouse
keywords: Alzheimer's disease; RNA-bindin protein; amyloid beta; amyloid precursor protein; forskolin