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Stabilization and Characterization of Cytotoxic Aβ40 Oligomers Isolated from an Aggregation Reaction in the Presence of Zinc Ions.

Accepted version
Peer-reviewed

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Type

Article

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Authors

Mannini, Benedetta 
Habchi, Johnny 
Chia, Sean 
Ruggeri, Francesco S 

Abstract

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.

Description

Keywords

Alzheimer’s disease, OC-positive aggregates, Protein oligomer aggregates, amyloid, antiparallel oligomer, metal ions, Alzheimer Disease, Amyloid beta-Peptides, Animals, Caenorhabditis elegans, Cell Line, Tumor, Cell Survival, Humans, In Vitro Techniques, Movement, Neuroblastoma, Neurons, Peptide Fragments, Polymers, Protein Aggregates, Protein Aggregation, Pathological, Protein Conformation, beta-Strand, Zinc

Journal Title

ACS Chem Neurosci

Conference Name

Journal ISSN

1948-7193
1948-7193

Volume Title

9

Publisher

American Chemical Society (ACS)
Sponsorship
Swiss National Science Foundation for Science (grant number P2ELP2_162116)