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

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• 作者：Pengfei Meng^a ; Hidemi Yoshida^a ; ^{hidemi_yoshida@gakushikai.jp} ; Tomoh Matsumiya^a ; Tadaatsu Imaizumi^a ; Kunikazu Tanji^b ; Fei Xing^a ; Ryo Hayakari^a ; Junichi Dempoya^c ; Tetsuya Tatsuta^d ; Tomomi Aizawa-Yashiro^e ; Junsei Mimura^f ; Kunio Kosaka^g ; Ken Itoh^f ; Kei Satoh^a
• 关键词：A¦Â ; amyloid-¦Â ; AD ; Alzheimer's disease ; ADAM ; a disintegrin and metalloproteinase ; APP ; amyloid precursor protein ; BACE1 ; ¦Â-site APP-cleaving enzyme-1 ; BCA ; bicinchoninic acid ; BSA ; bovine serum albumin ; CA ; carnosic acid ; CHAPS ; 3-[(3-Cholamidopropyl)
• 刊名：Neuroscience Research
• 出版年：2013
• 出版时间：February, 2013
• 年：2013
• 卷：75
• 期：2
• 页码：94-102
• 全文大小：894 K

文摘

A hallmark of Alzheimer's disease (AD) is the aggressive appearance of plaques of amyloid beta (A¦Â) peptides, which result from the sequential cleavage of amyloid precursor protein (APP) by the ¦Â- and ¦Ã-secretases. A¦Â production is evaded by alternate cleavage of APP by the ¦Á- and ¦Ã-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 A¦Â 1-42 peptide (A¦Â42) and on the expressions of the related genes in SH-SY5Y human neuroblastoma cells. The treatment of cells with CA suppressed A¦Â42 secretion (61 % suppression at 30 ¦ÌM). CA treatment enhanced the mRNA expressions of an ¦Á-secretase TACE (tumor necrosis factor-¦Á-converting enzyme, also called a disintegrin and metalloproteinase-17, ADAM17) significantly and another ¦Á-secretase ADAM10 marginally; however, the ¦Â-secretase BACE1 (¦Â-site APP-cleaving enzyme-1) was not increased by CA. Knockdown of TACE by siRNA reduced soluble-APP¦Á secretion enhanced by CA and partially recovered the CA-suppressed A¦Â42 secretion. These results suggest that CA reduces A¦Â42 production by activating TACE without promoting BACE1 in human neuroblastoma cells. The use of CA may have a potential in the prevention of A¦Â-mediated diseases, particularly AD.