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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
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.
ISSN: 10902104
Appears in Collections:Scopus 2011-2015

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