Carnosic acid suppresses the production of amyloid-β 1-42 and 1-43 by inducing an α-secretase TACE/ADAM17 in U373MG human astrocytoma cells.

Abstract

Amyloid beta (Aβ) peptides are key molecules in the pathogenesis of Alzheimer's disease (AD). The sequential cleavage of amyloid precursor protein (APP) by the β- and γ-secretases generates Aβ peptides; however, the alternate cleavage of APP by the α- and γ-secretases decreases Aβ production. We previously reported that carnosic acid (CA), a phenolic diterpene compound found in the labiate herbs rosemary and sage, suppresses Aβ (1-40 and 1-42) production by activating α-secretase in cultured SH-SY5Y human neuroblastoma cells (Neurosci. Res. 2013; 75: 94-102). Here, we investigated the effect of CA on the production of Aβ peptides (1-40, 1-42 and 1-43) in U373MG human astrocytoma cells. The treatment of cells with CA suppressed Aβ40/42/43 release (55-71% decrease at 50μM). 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); however, the β-secretase BACE1 (β-site APP-cleaving enzyme-1) was not increased by CA. Knockdown of TACE by siRNA reduced soluble-APPα release enhanced by CA and partially recovered the CA-suppressed Aβ40/42/43 release. These results suggest that CA reduces Aβ production, at least partially, by activating TACE in human astroglial cells. The use of CA may have a potential in the prevention of Aβ-mediated diseases.

• Authors: Hidemi Yoshida, Pengfei Meng, Tomoh Matsumiya, Kunikazu Tanji, Ryo Hayakari, Fei Xing, Liang Wang, Kazushi Tsuruga, Hiroshi Tanaka, Junsei Mimura, Kunio Kosaka, Ken Itoh, Ippei Takahashi, Tadaatsu Imaizumi
• Journal: Neuroscience research (Neurosci Res) Vol. 79 Pg. 83-93 (Feb 2014) ISSN: 1872-8111 [Electronic] Ireland
• PMID: 24295810 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Chemical References

• Abietanes
• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Peptide Fragments
• Plant Extracts
• amyloid beta-protein (1-42)
• amyloid beta-protein (1-43)
• Amyloid Precursor Protein Secretases
• ADAM Proteins
• ADAM17 Protein
• ADAM17 protein, human
• salvin

Topics

• ADAM Proteins (biosynthesis)
• ADAM17 Protein
• Abietanes (pharmacology)
• Amyloid Precursor Protein Secretases (metabolism)
• Amyloid beta-Peptides (biosynthesis)
• Amyloid beta-Protein Precursor (metabolism)
• Astrocytoma
• Cell Line, Tumor
• Humans
• Peptide Fragments (biosynthesis)
• Plant Extracts (pharmacology)