Mechanistic Insights of Curcumin Interactions with the Core-Recognition Motif of β-Amyloid Peptide
Mechanistic Insights of Curcumin Interactions with the Core-Recognition Motif of β-Amyloid Peptide
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DOI：
10.1021/jf4000709
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发表时间：
2013-04-03
影响因子：
6.1
通讯作者：
Krishnan, Uma Maheswari
中科院分区：
文献类型：
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作者：
Kumaraswamy, Priyadharshini;Sethuraman, Swaminathan;Krishnan, Uma Maheswari
阿尔茨海默病是一种神经退行性疾病，影响着全世界数百万人。淀粉样前体蛋白的蛋白水解裂解形成淀粉样β肽（A β（1-42）），其聚集形成老年斑。存在于A β（1-42）中的KLVFF基序对于聚集是必需的。姜黄素是姜黄中主要的姜黄素类化合物，对阿尔茨海默病有治疗作用。然而，A β（1-42）肽和姜黄素之间的相互作用的性质仍然未被探索。对核心识别基序KLVFF与姜黄素相互作用的研究可以外推以破译A β（1-42）与姜黄素之间的相互作用。我们的数据表明，姜黄素和KLVFF通过疏水力强烈相互作用，并通过氢键稳定。从相变温度的正移证实了疏水相互作用。荧光猝灭研究表明，静态猝灭机制。FTIR数据证实了姜黄素的β折叠断裂能力，这也通过细胞培养研究得到证实。
Alzheimer's disease is a neurodegenerative disease affecting millions of people worldwide. The proteolytic cleavage of amyloid precursor protein forms amyloid beta peptide (A beta(1-42)), which aggregates to form senile plaques. The KLVFF motif present in A beta(1-42) is essential for aggregation. Curcumin, a prinicipal curcuminoid present in turmeric, shows therapeutic activity against Alzheimer's disease. However, the nature of interaction between the A beta(1-42) peptide and curcumin remains unexplored. Studies on the interaction of the core-recognition motif KLVFF with curcumin can be extrapolated to decipher the interactions between A beta(1-42) and curcumin. Our data show that curcumin and KLVFF interact strongly through hydrophobic forces and are stabilized by hydrogen bonding. The hydrophobic interactions were confirmed from the positive shift in the phase transition temperature. Fluorescence quenching studies demonstrate a static quenching mechanism. FTIR data confirm the beta sheet breaking ability of curcumin, which is also substantiated by cell culture studies.