Publication: Activation of α-secretase by curcumin-aminoacid conjugates
Issued Date
2012-08-10
Resource Type
ISSN
10902104
0006291X
0006291X
Other identifier(s)
2-s2.0-84864813737
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Mahidol University
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SCOPUS
Bibliographic Citation
Biochemical and Biophysical Research Communications. Vol.424, No.4 (2012), 691-696
Suggested Citation
Ramesh B. Narasingapa, Manjunatha R. Jargaval, Srinivas Pullabhatla, Htut Htut Htoo, Jagannatha K.S. Rao, Jean François Hernandez, Piyarat Govitrapong, Bruno Vincent Activation of α-secretase by curcumin-aminoacid conjugates. Biochemical and Biophysical Research Communications. Vol.424, No.4 (2012), 691-696. doi:10.1016/j.bbrc.2012.07.010 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/13640
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Title
Activation of α-secretase by curcumin-aminoacid conjugates
Abstract
The extracellular senile plaques observed in Alzheimer's disease (AD) patients are mainly composed of amyloid peptides produced from the β-amyloid precursor protein (βAPP) by β- and γ-secretases. A third non-amyloidogenic α-secretase activity performed by the disintegrins ADAM10 and ADAM17 occurs in the middle of the amyloid-β peptide Aβ and liberates the large sAPPα neuroprotective fragment. Since the activation of α-secretase recently emerged as a promising therapeutic approach to treat AD, the identification of natural compounds able to trigger this cleavage is highly required. Here we describe new curcumin-based modified compounds as α-secretase activators. We established that the aminoacid conjugates curcumin-isoleucine, curcumin-phenylalanine and curcumin-valine promote the constitutive α-secretase activity and increase ADAM10 immunoreactivity. Strickingly, experiments carried out under conditions mimicking the PKC/muscarinic receptor-regulated pathway display different patterns of activation by these compounds. Altogether, our data identified new lead natural compounds for the future development of powerful and stable α-secretase activators and established that some of these molecules are able to discriminate between the constitutive and regulated α-secretase pathways. © 2012 Elsevier Inc.