Paper Citing NAMD - Abstract
Ormeno, David; Romero, Fernando; Lopez-Fenner, Julio; Avila, Andres; Martinez-Torres, Ataulfo; Parodi, Jorge
Ethanol Reduces Amyloid Aggregation In Vitro and Prevents Toxicity in Cell Lines
ARCHIVES OF MEDICAL RESEARCH, 44:1-7, JAN 2013
Background. Alzheimer's disease (AD) alters cognitive functions. A mixture of soluble beta-amyloid aggregates (A beta) are known to act as toxic agents. It has been suggested that moderate alcohol intake reduces the development of neurodegenerative diseases, but the molecular mechanisms leading to this type of prevention have been elusive. We show the ethanol effect in the generation of complex A beta in vitro and the impact on the viability of two cell lines. Methods. The effect of ethanol on the kinetics of beta-amyloid aggregation in vitro was assessed by turbimetry. Soluble- and ethanol-treated beta-amyloid were added to the cell lines HEK and PC-12 to compare their effects on metabolic activity using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. In addition, we used molecular modeling to assess the impact of exposure to ethanol on the structure of beta-amyloid. Results. Exposure to soluble beta-amyloid was toxic to both cell lines; however, exposing the cells to beta-amyloid aggregated in 10 mmol ethanol prevented the effect. In silico modeling suggested that ethanol alters the dynamics for assembling A beta by disrupting a critical salt bridge between residues Asp 23 and Lys 28, required for amyloid dimerization. Thus, ethanol prevented the formation of complex short (similar to 100 nm) A beta, which are related to higher cell toxicity. Conclusions. Ethanol prevents the formation of stable AD dimers in vitro, thus protecting the cells maintained in culture. Accordingly, in silico modelling predicts that soluble beta-amyloid molecules do not form stable multimers when exposed to ethanol. (C) 2013 IMSS. Published by Elsevier Inc.
