NMR Studies of the Ion Channel-Forming Human Amyloid-β with Zinc Ion Concentrations

Alzheimer's disease (AD) is classified as an amyloid-related disease. Amyloid beta (A beta) is a transmembrane protein known to play a major role in the pathogenesis of AD. These A beta proteins can form ion channels or pores in the cell membrane. Studies have elucidated the structure of the transmembrane domain of A beta ion channels. In addition, various studies have investigated substances that block or inhibit the formation of A beta ion channels. Zinc ions are considered as potential inhibitors of AD. In this study, we focused on the transmembrane domain and some external domains of the A beta protein (hAPP-TM), and solution-state NMR was used to confirm the effect on residues of the protein in the presence of zinc ions. In addition, we sought to confirm the structure and orientation of the protein in the presence of the bicelle using solid-state NMR.