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: Francesca Lattanzio, Lucia Carboni, Donatella Carretta, Sanzio Candeletti, Patrizia Romualdi
• Journal: Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie (Exp Toxicol Pathol) Vol. 68 Issue 5 Pg. 271-6 (May 2016) ISSN: 1618-1433 [Electronic] Germany
• PMID: 26915812 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier GmbH. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Brain-Derived Neurotrophic Factor
• NIMA-Interacting Peptidylprolyl Isomerase
• Peptide Fragments
• amyloid beta-protein (25-35)
• BDNF protein, human
• SIRT1 protein, human
• Sirtuin 1
• PIN1 protein, human

Topics

• Alzheimer Disease (metabolism, physiopathology)
• Amyloid beta-Peptides (pharmacology)
• Blotting, Western
• Brain-Derived Neurotrophic Factor (metabolism, physiology)
• Cell Line, Tumor
• Humans
• NIMA-Interacting Peptidylprolyl Isomerase (metabolism, physiology)
• Neuroblastoma (metabolism)
• Peptide Fragments (pharmacology)
• Real-Time Polymerase Chain Reaction
• Sirtuin 1 (metabolism, physiology)