Abstract
A major cause for cellular toxicity involved in the onset of several neurodegenerative diseases is the aberrant aggregation of peptides or proteins into oligomers and eventually fibrils. In the case of Alzheimer’s disease, the main aggregating peptide is the amyloid β-peptide with two main alloforms of 40 (Aβ40) and 42 (Aβ42) amino acids. Numerous experimental studies have shown that early oligomers on-pathway to fibril formation are toxic, with Aβ42 showing a higher toxicity than Aβ40. To explore the aggregation mechanisms and differences in the oligomeric conformations we follow the aggregation of Aβ40 and Aβ42 from isolated monomers using all-atom molecular dynamics simulations. We describe the kinetics of aggregation and differences in the pathways arising from sequence differences using transition networks.This chapter is partly adapted from Barz et al. (J Phys Chem B 118(4):1003, 2014; Chem Commun 50:5373, 2014) with permission from the American Chemical Society and The Royal Society of Chemistry, respectively.
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Acknowledgements
We gratefully acknowledge the computing time granted on the supercomputer JUROPA at Jülich Supercomputing Centre. We thank Prof. David J. Wales and Dr. Olujide O. Olubiyi for fruitful discussions.
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Barz, B., Strodel, B. (2015). Thermodynamics and Kinetics of Amyloid Aggregation from Atomistic Simulations. In: Olivares-Quiroz, L., Guzmán-López, O., Jardón-Valadez, H. (eds) Physical Biology of Proteins and Peptides. Springer, Cham. https://doi.org/10.1007/978-3-319-21687-4_2
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DOI: https://doi.org/10.1007/978-3-319-21687-4_2
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