title: Soluble beta-amyloid peptides, but not insoluble fibrils, have specific effect on neuronal microRNA expression.
abstract: Recent studies indicate that soluble β-amyloid (sAβ) oligomers, rather than their fibrillar aggregates, contribute to the pathogenesis of Alzheimer's disease (AD), though the mechanisms of their neurotoxicity are still elusive. Here, we demonstrate that sAβ derived from 7PA2 cells exert a much stronger effect on the regulation of a set of functionally validated microRNAs (miRNAs) in primary cultured neurons than the synthetic insoluble Aβ fibrils (fAβ). Synthetic sAβ peptides at a higher concentration present comparable effect on these miRNAs in our neuronal model. Further, the sAβ-induced miR-134, miR-145 and miR-210 expressions are fully reversed by two selective N-methyl-d-aspartate (NMDA) receptor inhibitors, but are neither reversed by insulin nor by forskolin, suggesting an NMDA receptor-dependent, rather than PI3K/AKT or PKA/CREB signaling dependent regulatory mechanism. In addition, the repression of miR-107 expression by the sAβ containing 7PA2 CM is likely involved multiple mechanisms and multiple players including NMDA receptor, N-terminally truncated Aβ and reactive oxygen species (ROS).
authors.affiliation: Department of Pharmacology, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Jing Jing
authors.initials: JJ
authors.lastname: Li
authors.affiliation: Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, United States of America.
authors.forename: Georgia
authors.initials: G
authors.lastname: Dolios
authors.affiliation: Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, United States of America.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Francesca-Fang
authors.initials: FF
authors.lastname: Liao
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D007328:Insulin / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction; D012995:Solubility
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D017362:Cyclic AMP Response Element-Binding Protein; D007328:Insulin; D035683:MicroRNAs; D016194:Receptors, N-Methyl-D-Aspartate; D019869:Phosphatidylinositol 3-Kinases; D017868:Cyclic AMP-Dependent Protein Kinases