P006 - THE LUMINESCENT CONJUGATED OLIGOTHIOPHENE H-FTAA ATTENUATES TOXICITY OF THE AMYLOID-BETA PEPTIDE WITH THE ARCTIC MUTATION
Abstract
Aims
The prevailing opinion is that prefibrillar β-amyloid (Aβ) species, rather than end-stage amyloid fibrils cause neuronal dysfunction in Alzheimer’s disease, although the mechanisms behind Aβ neurotoxicity remain to be elucidated. Luminescent conjugated oligothiophenes (LCOs) have spectral properties upon binding to amyloid proteins and have previously been reported to change the toxicity of Aβ1-42 and prion protein. The aim of this study was to investigate whether the LCOs h-FTAA and p-FTAA could change the toxicity of Aβ with the Arctic mutation (AβArc).
Methods
A panel of cell biology techniques as well as biophysical methods i.e. Thioflavin T (ThT) assay, transmission electron microscopy and binding assays were used.
Results
Cell viability assays demonstrated that AβArc toxicity on neuroblastoma cells declined with increased time of aggregation. Interestingly, h-FTAA but not p-FTAA, rescued the AβArc-mediated toxicity. Aggregation kinetics of AβArc using ThT, h-FTAA and p-FTAA showed differences after 5 h, which suggest that ThT, h-FTAA and p-FTAA may affect the aggregation process in different ways. Furthermore, a binding assay of AβArc bound to either h-FTAA or p-FTAA demonstrated different binding affinity of h-FTAA and p-FTAA to AβArc which might explain the diverse protective ability of h-FTAA and p-FTAA to AβArc-mediated toxicity.
Conclusions
In conclusion, we show that h-FTAA but not p-FTAA attenuates toxicity of AβArc. This protection probably depends on specific interactions between h-FTAA and AβArc that cannot be formed by p-FTAA. These results indicate that h-FTAA might have a therapeutic potential for familial Alzheimer’s disease caused by the Arctic mutation.
