Exploration of lycorine and copper(II)'s association with the N-Terminal domain of amyloid β

Lycorine (LYC) is an active alkaloid first isolated from Narcissus pseudonarcissus and found in most Amaryllidaceae plants. It belongs to the same family as galantamine, which is the active component of a drug used for the treatment of Alzheimer's disease. Similarly to galantamine, LYC is able to suppress induced amyloid beta (A beta) toxicity in differentiated SH-SY5Y cell lines and it can weakly interact with the N-terminal region of A beta via electrostatic interactions. The N-terminal A beta domain is also involved in Cu(II)/Cu(I) binding and the formed complexes are known to play a key role in ROS production. In this study, the A beta-LYC interaction in the absence and in the presence of copper ions was investigated by using the N-terminal A beta peptide encompassing the first 16 residues. NMR analysis showed that A beta can simultaneously interact with Cu(II) and LYC. The Cu(II) binding mode remains unchanged in the presence of LYC, while LYC association is favored when an A beta-Cu(II) complex is formed. Moreover, UV-VIS studies revealed the ability of LYC to interfere with the catalytic activities of the A beta-Cu(II) complexes by reducing the ascorbate consumption monitored at 265 nm.