Alzheimer's disease and cigarette smoke components: effects of nicotine, PAHs, and Cd(II), Cr(III), Pb(II), Pb(IV) ions on amyloid-? peptide aggregation.
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ABSTRACT: Cigarette smoking is a significant risk factor for Alzheimer's disease (AD), which is associated with extracellular brain deposits of amyloid plaques containing aggregated amyloid-? (A?) peptides. A? 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? 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? aggregation process. Cd(II), Cr(III), and Pb(II) ions displayed general electrostatic interactions with A?, whereas Pb(IV) ions showed specific transient binding coordination to the N-terminal A? segment. Thus, Pb(IV) ions are especially prone to interact with A? and affect its aggregation. While Pb(IV) ions affected mainly A? 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?, nor did it affect A? aggregation. Our A? 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.
SUBMITTER: Wallin C
PROVIDER: S-EPMC5663743 | biostudies-literature | 2017 Oct
REPOSITORIES: biostudies-literature
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