Amyloid β cytotoxicity is enhanced or reduced depending on formation of amyloid β oligomeric forms

Objectives We explored the underlying mechanisms that facilitate reducing and enhancing effects of exogenous proteins on cytotoxicity of amyloid beta (A beta), a main pathogen of Alzheimer's disease, by using anEscherichia colichaperonin DnaK. Results DnaK was chosen as a tool, because it, easily available and functionally stable, reduced or enhanced A beta cytotoxicity depending on its concentration. Cytotoxicity was enhanced when the molar ratio of DnaK to A beta 42, at 20 mu M A beta 42, was 0.01-0.5, while reduced cytotoxicity was observed at higher ratios (> 1) at 1 mu M A beta 42. Significant amounts of oligomeric A beta 42 species accumulated concomitantly with enhanced cytotoxicity, whereas the oligomers appeared to form complexes with DnaK in conditions of reduced cytotoxicity. Conclusions The difference in cytotoxicity was due to variations in the toxic oligomeric A beta species and DnaK is a useful tool for the study of the A beta ultrastructure formation and toxicity of A beta peptide.

Automated summary

The Escherichia coli chaperonin DnaK can reduce or enhance the cytotoxicity of amyloid beta (Aβ) depending on its concentration. High ratios of DnaK to Aβ42 result in toxic oligomeric Aβ species accumulation and formation of complexes, while lower ratios lead to reduced cytotoxicity. DnaK is a useful tool for studying the ultrastructure formation and toxicity of Aβ peptide.