Activation of alpha-secretase by curcumin-aminoacid conjugates.

Ramesh, B. N. and Manjunatha, R. Jargaval and Srinivas, P. and Htoo, H. H. and Jagannatha Rao, K. S. and Hernandez, J. F. and Govitrapong, P. and Vincent, B. (2012) Activation of alpha-secretase by curcumin-aminoacid conjugates. Biochemical and Biophysical Research Communications, 424 (4). pp. 691-696.

PDF Biochemical and Biophysical Research Communications, Volume 424, Issue 4, 10 August 2012, Pages 691-696.pdf - Published Version Restricted to Registered users only Download (680kB)

Abstract

The extracellular senile plaques observed in Alzheimer’s disease (AD) patients are mainly composed of amyloid peptides produced from the b-amyloid precursor protein (bAPP) by b- and c-secretases. A third non-amyloidogenic a-secretase activity performed by the disintegrins ADAM10 and ADAM17 occurs in the middle of the amyloid-b peptide Ab and liberates the large sAPPa neuroprotective fragment. Since the activation of a-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 a-secretase activators. We established that the aminoacid conjugates curcumin–isoleucine, curcumin–phenylalanine and curcumin–valine promote the constitutive a-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 a-secretase activators and established that some of these molecules are able to discriminate between the constitutive and regulated a-secretase pathways

Item Type:	Article
Uncontrolled Keywords:	Curcumin, Alzheimer, bAPP alpha-Secretase, Disintegrins, Muscarinic receptors
Subjects:	500 Natural Sciences and Mathematics > 07 Life Sciences > 03 Biochemistry & Molecular Biology > 18 Phytochemistry
Divisions:	Plantation Products Spices and Flavour Technology
Depositing User:	Food Sci. & Technol. Information Services
Date Deposited:	27 Aug 2012 04:40
Last Modified:	25 Sep 2018 11:02
URI:	http://ir.cftri.res.in/id/eprint/10956

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