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|Title:||Activation of α-secretase by curcumin-aminoacid conjugates|
|Authors:||Ramesh B. Narasingapa|
Manjunatha R. Jargaval
Htut Htut Htoo
Jagannatha K.S. Rao
Jean François Hernandez
Central Food Technological Research Institute India
|Keywords:||Biochemistry, Genetics and Molecular Biology|
|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.|
|Appears in Collections:||Scopus 2011-2015|
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