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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/13640
Title: Activation of α-secretase by curcumin-aminoacid conjugates
Authors: Ramesh B. Narasingapa
Manjunatha R. Jargaval
Srinivas Pullabhatla
Htut Htut Htoo
Jagannatha K.S. Rao
Jean François Hernandez
Piyarat Govitrapong
Bruno Vincent
Mahidol University
Central Food Technological Research Institute India
INDICASAT-AIP
Jain University
Jain University
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 10-Aug-2012
Citation: Biochemical and Biophysical Research Communications. Vol.424, No.4 (2012), 691-696
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.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84864813737&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/13640
ISSN: 10902104
0006291X
Appears in Collections:Scopus 2011-2015

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