Background: Alzheimer's is a complex neurodegenerative disease and is characterized by extraneuronal accumulation of β-amyloid peptide. Because of its complex nature, multi-target directed ligands (MTDLs) are increasingly being considered as promising anti-Alzheimer therapeutic agents. This study is aimed at determining the effects of Cassia tora ethyl acetate fraction on several Alzheimer-associated deleterious events in test tubes as well as in human neuroblastoma SK-N-SH and SH-SY5Y cell lines.
Method: Ethyl acetate fraction of C. tora was purified by chromatography, characterized by H and C NMR, and tested for its ability to prevent Aβ aggregation by thioflavin-T fluorescence and transmission electron microscopy. We also analyzed the intracellular ROS level and cytotoxicity in SK-N-SH and SH-SY5Y cell lines.
Results: The extract inhibits the formation of Aβ aggregation from monomers and oligomers, as also acetylcholinesterase activity, Aβ -induced cell death, and Aβ -dependent intracellular ROS production in both SK-N-SH and SH-SY5Y cells. In-depth chromatographic and spectroscopic analysis of the extract revealed that the active molecules are most likely triglycerides of oleic acid (CHO).
Conclusion: We demonstrate for the first time that Cassia tora fraction prevents Aβ aggregation, inhibits acetylcholinesterase and alleviates Aβ -induced oxidative stress in human neuroblastoma cells. We further suggest the possible use of triglycerides of oleic acid as efficient anti-Alzheimer agents.
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http://dx.doi.org/10.1016/j.pharep.2019.06.014 | DOI Listing |
J Biol Chem
December 2018
From the Department of Biology, Faculty of Science and Engineering and
ClpB, a bacterial homologue of heat shock protein 104 (Hsp104), can disentangle aggregated proteins with the help of the DnaK, a bacterial Hsp70, and its co-factors. As a member of the expanded superfamily of ATPases associated with diverse cellular activities (AAA), ClpB forms a hexameric ring structure, with each protomer containing two AAA modules, AAA1 and AAA2. A long coiled-coil middle domain (MD) is present in the C-terminal region of the AAA1 and surrounds the main body of the ring.
View Article and Find Full Text PDFBiosci Rep
December 2017
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, U.S.A.
Front Mol Biosci
February 2017
Center for Molecular Biology of the Heidelberg University, German Cancer Research Center Heidelberg, Germany.
The members of the hexameric AAA+ disaggregase of and , ClpB, and Hsp104, cooperate with the Hsp70 chaperone system in the solubilization of aggregated proteins. Aggregate solubilization relies on a substrate threading activity of ClpB/Hsp104 fueled by ATP hydrolysis in both ATPase rings (AAA-1, AAA-2). ClpB/Hsp104 ATPase activity is controlled by the M-domains, which associate to the AAA-1 ring to downregulate ATP hydrolysis.
View Article and Find Full Text PDFJ Biol Chem
April 2015
From the Department of Biology, Faculty of Science and Engineering and the Institute for Integrative Neurobiology, Konan University, Okamoto 8-9-1, Kobe 658-8501, Japan
FEBS J
July 2011
Department of Biology, Faculty of Science and Engineering, Konan University, Okamoto, Kobe, Japan.
ClpB, a member of the expanded superfamily of ATPases associated with diverse cellular activities (AAA+), forms a ring-shaped hexamer and cooperates with the DnaK chaperone system to reactivate aggregated proteins in an ATP-dependent manner. The ClpB protomer consists of an N-terminal domain, an AAA+ module (AAA-1), a middle domain, and a second AAA+ module (AAA-2). Each AAA+ module contains highly conserved WalkerA and WalkerB motifs, and two arginines (AAA-1) or one arginine (AAA-2).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!