Stabilization and Characterization of Cytotoxic Aβ40 Oligomers Isolated from an Aggregation Reaction in the Presence of Zinc Ions.
Ruggeri, Francesco S
Dobson, Christopher M
ACS Chem Neurosci
American Chemical Society (ACS)
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Mannini, B., Habchi, J., Chia, S., Ruggeri, F. S., Perni, M., Knowles, T. P., Dobson, C. M., & et al. (2018). Stabilization and Characterization of Cytotoxic Aβ40 Oligomers Isolated from an Aggregation Reaction in the Presence of Zinc Ions.. ACS Chem Neurosci, 9 (12), 2959-2971. https://doi.org/10.1021/acschemneuro.8b00141
Small oligomers formed during the aggregation of certain peptides and proteins are highly cytotoxic in numerous neurodegenerative disorders. Because of their transient nature and conformational heterogeneity, however, the structural and biological features of these oligomers are still poorly understood. Here, we describe a method of generating stable oligomers formed by the Alzheimer's Aβ40 peptide by carrying out an aggregation reaction in the presence of zinc ions. The resulting oligomers are amenable to detailed biophysical and biological characterization, which reveals a homogeneous population with small size, high cross-β sheet structure content, and extended hydrophobic surface patches. We also show that these oligomers decrease the viability of neuroblastoma cells and impair the motility of C. elegans. The availability of these oligomers offers novel opportunities for studying the mechanisms of Aβ40 toxicity in vitro and in cellular and animal models of Alzheimer's disease.
Neurons, Cell Line, Tumor, Animals, Humans, Caenorhabditis elegans, Neuroblastoma, Alzheimer Disease, Zinc, Polymers, Peptide Fragments, Cell Survival, Movement, Amyloid beta-Peptides, In Vitro Techniques, Protein Aggregates, Protein Aggregation, Pathological, Protein Conformation, beta-Strand
Swiss National Science Foundation for Science (grant number P2ELP2_162116)
External DOI: https://doi.org/10.1021/acschemneuro.8b00141
This record's URL: https://www.repository.cam.ac.uk/handle/1810/284475