title: Treatment with the neurotoxic Aβ (25-35) peptide modulates the expression of neuroprotective factors Pin1, Sirtuin 1, and brain-derived neurotrophic factor in SH-SY5Y human neuroblastoma cells.
abstract: The deposition of Amyloid β peptide plaques is a pathological hallmark of Alzheimer's disease (AD). The Aβ (25-35) peptide is regarded as the toxic fragment of full-length Aβ (1-42). The mechanism of its toxicity is not completely understood, along with its contribution to AD pathological processes. The aim of this study was to investigate the effect of the neurotoxic Aβ (25-35) peptide on the expression of the neuroprotective factors Pin1, Sirtuin1, and Bdnf in human neuroblastoma cells. Levels of Pin1, Sirtuin 1, and Bdnf were compared by real-time PCR and Western blotting in SH-SY5Y cells treated with Aβ (25-35) or administration vehicle. The level of Pin1 gene and protein expression was significantly decreased in cells exposed to 25 μM Aβ (25-35) compared to vehicle-treated controls. Similarly, Sirtuin1 expression was significantly reduced by Aβ (25-35) exposure. In contrast, both Bdnf mRNA and protein levels were significantly increased by Aβ (25-35) treatment, suggesting the activation of a compensatory response to the insult. Both Pin1 and Sirtuin 1 exert a protective role by reducing the probability of plaque deposition, since they promote amyloid precursor protein processing through non-amyloidogenic pathways. The present results show that Aβ (25-35) peptide reduced the production of these neuroprotective proteins, thus further increasing Aβ generation.
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, via Irnerio 48, 40126 Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lattanzio
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, via Irnerio 48, 40126 Bologna, Italy. Electronic address: lucia.carboni4@unibo.it.
authors.forename: Lucia
authors.initials: L
authors.lastname: Carboni
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, via Irnerio 48, 40126 Bologna, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Carretta
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, via Irnerio 48, 40126 Bologna, Italy.
authors.forename: Sanzio
authors.initials: S
authors.lastname: Candeletti
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, via Irnerio 48, 40126 Bologna, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Romualdi
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D006801:Humans; D000072340:NIMA-Interacting Peptidylprolyl Isomerase / Q000378:metabolism / Q000502:physiology*; D009447:Neuroblastoma / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000378:metabolism / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C579455:BDNF protein, human; C447939:SIRT1 protein, human; D056564:Sirtuin 1; C000606846:PIN1 protein, human
keywords: Amyloid β; Brain-derived neurotrophic factor; Pin1; SH-SY5Y cells; Sirtuin 1