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.
journal_name
Neurosci Resjournal_title
Neuroscience researchauthors
Yoshida H,Meng P,Matsumiya T,Tanji K,Hayakari R,Xing F,Wang L,Tsuruga K,Tanaka H,Mimura J,Kosaka K,Itoh K,Takahashi I,Imaizumi Tdoi
10.1016/j.neures.2013.11.004subject
Has Abstractpub_date
2014-02-01 00:00:00pages
83-93eissn
0168-0102issn
1872-8111pii
S0168-0102(13)00261-7journal_volume
79pub_type
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