Carnosic acid suppresses the production of amyloid-β 1-42 by inducing the metalloprotease gene TACE/ADAM17 in SH-SY5Y human neuroblastoma cells.

Abstract

A hallmark of Alzheimer's disease (AD) is the aggressive appearance of plaques of amyloid beta (Aβ) peptides, which result from the sequential cleavage of amyloid precursor protein (APP) by the β- and γ-secretases. Aβ production is evaded by alternate cleavage of APP by the α- and γ-secretases. Carnosic acid (CA) has been proven to activate the transcription factor Nrf2, a main regulator of the antioxidant response. We investigated the effects of CA on the production of Aβ 1-42 peptide (Aβ42) and on the expressions of the related genes in SH-SY5Y human neuroblastoma cells. The treatment of cells with CA suppressed Aβ42 secretion (61% suppression at 30μM). CA treatment enhanced the mRNA expressions of an α-secretase TACE (tumor necrosis factor-α-converting enzyme, also called a disintegrin and metalloproteinase-17, ADAM17) significantly and another α-secretase ADAM10 marginally; however, the β-secretase BACE1 (β-site APP-cleaving enzyme-1) was not increased by CA. Knockdown of TACE by siRNA reduced soluble-APPα secretion enhanced by CA and partially recovered the CA-suppressed Aβ42 secretion. These results suggest that CA reduces Aβ42 production by activating TACE without promoting BACE1 in human neuroblastoma cells. The use of CA may have a potential in the prevention of Aβ-mediated diseases, particularly AD.

• Authors: Pengfei Meng, Hidemi Yoshida, Tomoh Matsumiya, Tadaatsu Imaizumi, Kunikazu Tanji, Fei Xing, Ryo Hayakari, Junichi Dempoya, Tetsuya Tatsuta, Tomomi Aizawa-Yashiro, Junsei Mimura, Kunio Kosaka, Ken Itoh, Kei Satoh
• Journal: Neuroscience research (Neurosci Res) Vol. 75 Issue 2 Pg. 94-102 (Feb 2013) ISSN: 1872-8111 [Electronic] Ireland
• PMID: 23257508 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Chemical References

• APP protein, human
• Abietanes
• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Membrane Proteins
• Peptide Fragments
• Plant Extracts
• amyloid beta-protein (1-42)
• Amyloid Precursor Protein Secretases
• ADAM Proteins
• ADAM17 Protein
• ADAM17 protein, human
• salvin

Topics

• ADAM Proteins (metabolism)
• ADAM17 Protein
• Abietanes (pharmacology)
• Alzheimer Disease (enzymology, genetics)
• Amyloid Precursor Protein Secretases (genetics, metabolism)
• Amyloid beta-Peptides (metabolism)
• Amyloid beta-Protein Precursor (metabolism)
• Cell Line, Tumor
• Humans
• Membrane Proteins (metabolism)
• Neurons (metabolism)
• Peptide Fragments (metabolism)
• Plant Extracts (pharmacology)