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Transition Metal Ion Interactions with Disordered Amyloid-β Peptides in the Pathogenesis of Alzheimer´s Disease: Insights from Computational Chemistry Studies.

08:00 EDT 1st April 2019 | BioPortfolio

Summary of "Transition Metal Ion Interactions with Disordered Amyloid-β Peptides in the Pathogenesis of Alzheimer´s Disease: Insights from Computational Chemistry Studies."

Monomers and oligomers of the amyloid-β peptide aggregate to form the fibrils found in the brains of Alzheimer´s disease patients. These monomers and oligomers are largely disordered and can interact with transition metal ions, affecting the mechanism and kinetics of amyloid-β aggregation. Due to the disordered nature of amyloid-β, its rapid aggregation, as well as solvent and paramagnetic effects, experimental studies face challenges in the characterization of transition metal ions bound to amyloid-β monomers and oligomers. The details of the coordination chemistry between transition metals and amyloid-β obtained from experiments remain debated. Furthermore, the impact of transition metal ion binding on the mon-omeric or oligomeric amyloid-β structures and dynamics are still poorly understood. Computational chemistry studies can serve as an important complement to experimental studies, and can provide additional knowledge on the binding between amyloid-β and transition metal ions. Many research groups conducted first principles calculations, ab initio molecular dy-namics simulations, quantum mechanics/classical mechanics simulations and classical molecular dynamics simulations for studying the interplay between transition metal ions and amyloid-β monomers and oligomers. This review summarizes the current understanding of transition metal interactions with amyloid-β obtained from computational chemistry studies. We also emphasize the current view of the coordination chemistry between transition metal ions and amyloid-β. This infor-mation represents an important foundation for future metal ion chelator and drug design studies aiming to combat Alz-heimer's disease.

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This article was published in the following journal.

Name: Journal of chemical information and modeling
ISSN: 1549-960X
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Proteins that form the core of amyloid fibrils. For example, the core of amyloid A is formed from amyloid A protein, also known as serum amyloid A protein or SAA protein.

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