Journal
CHEMISTRY-A EUROPEAN JOURNAL
Volume 22, Issue 34, Pages 11967-11970Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201601763
Keywords
aggregation; Alzheimer's disease; amyloid beta peptide; chirality; neurotoxicity
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Funding
- NIH [S10OD016246-01A1]
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The amyloid beta peptide 42 (A beta 42) is an aggregation-prone peptide that plays a pivotal role in Alzheimer's disease. We report that a subtle perturbation to the peptide through a single chirality change at glutamate 22 leads to a pronounced delay in the beta-sheet adoption of the peptide. This was accompanied by an attenuated propensity of the peptide to form fibrils, which was correlated with changes at the level of the fibrillary architecture. Strikingly, the incorporation of D-glutamate was found to stabilize a soluble, ordered macromolecular assembly with enhanced cytotoxicity to PC12 cells, highlighting the importance of advanced prefibrillary A beta aggregates in neurotoxicity.
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