Alzheimer's disease and cigarette smoke components: effects of nicotine, PAHs, and Cd(II), Cr(III), Pb(II), Pb(IV) ions on amyloid-beta peptide aggregation

作者：Wallin Cecilia; Sholts Sabrina B; Osterlund Nicklas; Luo Jinghui; Jarvet Juri; Roos Per M; Ilag Leopold; Graslund Astrid; Warmlander Sebastian K T S^*

来源：Scientific Reports, 2017, 7(1): 14423.

DOI：10.1038/s41598-017-13759-5

extracellular brain deposits of amyloid plaques containing aggregated amyloid-beta (A beta) peptides. A beta aggregation occurs via multiple pathways that can be influenced by various compounds. Here, we used AFM imaging and NMR, fluorescence, and mass spectrometry to monitor in vitro how A beta aggregation is affected by the cigarette-related compounds nicotine, polycyclic aromatic hydrocarbons (PAHs) with one to five aromatic rings, and the metal ions Cd(II), Cr(III), Pb(II), and Pb(IV). All PAHs and metal ions modulated the A beta aggregation process. Cd(II), Cr(III), and Pb(II) ions displayed general electrostatic interactions with A beta, whereas Pb(IV) ions showed specific transient binding coordination to the N-terminal A beta segment. Thus, Pb(IV) ions are especially prone to interact with A beta and affect its aggregation. While Pb(IV) ions affected mainly A beta dimer and trimer formation, hydrophobic toluene mainly affected formation of larger aggregates such as tetramers. The uncharged and hydrophilic nicotine molecule showed no direct interactions with A beta, nor did it affect A beta aggregation. Our A beta interaction results suggest a molecular rationale for the higher AD prevalence among smokers, and indicate that certain forms of lead in particular may constitute an environmental risk factor for AD.

• 出版日期2017-10-31