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Carnosic acid suppresses the production of amyloid-β 1–42 by inducing the metalloprotease gene TACE/ADAM17 in SH-SY5Y human neuroblastoma cells
- Source :
- Neuroscience Research. 75:94-102
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
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.
- Subjects :
- SH-SY5Y
Amyloid beta
ADAM10
ADAM17 Protein
Amyloid beta-Protein Precursor
chemistry.chemical_compound
Alzheimer Disease
Cell Line, Tumor
Amyloid precursor protein
Humans
Secretion
Neurons
Gene knockdown
Amyloid beta-Peptides
biology
Plant Extracts
General Neuroscience
Membrane Proteins
Carnosic acid
General Medicine
Molecular biology
Peptide Fragments
ADAM Proteins
chemistry
Abietanes
biology.protein
Amyloid Precursor Protein Secretases
Subjects
Details
- ISSN :
- 01680102
- Volume :
- 75
- Database :
- OpenAIRE
- Journal :
- Neuroscience Research
- Accession number :
- edsair.doi.dedup.....65d971107de316b3d95fb3e79b0bcd4e