Is there a sodium effect in fibrillar amyloid-β oligomers?
© Horn et al; licensee Chemistry Central Ltd. 2014
Published: 11 March 2014
Hall mark in Alzheimer’s Disease (AD) is the aggregation of amyloid-β (Aβ) peptide into oligomers and fibrils. Nowadays, the soluble oligomers are believed to be the most neurotoxic species, probably the causative agents in AD. Amyloid-beta fibrils on the other hand may serve as reservoirs for small toxic oligomers. While it is well known from experiment, that the aggregation process is modulated by salt concentration in solution, the molecular details of the underlying interactions are not.
Salts occur ubiquitously in physiological environments and are known to have profound effects on the solubility of proteins (Hofmeister series). Monovalent alkali metal ions exhibit a more subtle effect on Aβ aggregation in experiment than doubly charged species [1, 2].
In this contribution we investigate the presence of the so-called ‘sodium-effect’ in fibrillar Aβ oligomers. This effect was originally described for dendrimer micelles formation modulating the self-organization of amphiphilic carboxylates: Na+ forms bridging complexes with carboxylate groups, in contrast to K+ .
Molecular dynamics simulations for a systematic series of single and double layer fibrillar Aβ oligomers in aqueous 150mM salt solution provide insights about the stabilizing interactions between the cations and charged Aβ key residues (e.g. Glu22). Comparison with a previous computational study at low ion concentration  show similarities and differences on a structural level. Interestingly, ions access the Aβ water channel region via entry paths suggested previously .
- Mantyh PW, Ghilardi JR, Rogers S, DeMaster E, Allen CJ, Stimson ER, Maggio JE: Aluminum, iron, and zinc ions promote aggregation of physiological concentrations of beta-amyloid peptide. J Neurochem. 1993, 61: 1171-1174. 10.1111/j.1471-4159.1993.tb03639.x.View ArticleGoogle Scholar
- Klement K, Wieligmann K, Meinhardt J, Hortschansky P, Richter W, Fändrich MJ: Effect of different salt ions on the propensity of aggregation and on the structure of Alzheimer's abeta(1-40) amyloid fibrils. Mol Biol. 2007, 373: 1321-1333. 10.1016/j.jmb.2007.08.068.View ArticleGoogle Scholar
- Rosenlehner K, Schade B, Böttcher C, Jäger CM, Clark T, Heinemann FW, Hirsch A: Sodium effect on self-organization of amphiphilic carboxylates: formation of structured micelles and superlattices. Chem Eur J. 2010, 16: 9544-9554. 10.1002/chem.201001150.View ArticleGoogle Scholar
- Kahler A, Sticht H, Horn AHC: Conformational Stability of Fibrillar Amyloid-Beta Oligomers via Protofilament Pair Formation – A Systematic Computational Study. PLoS ONE. 2013, 8: e70521-10.1371/journal.pone.0070521.View ArticleGoogle Scholar
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