The Luminescent Conjugated Oligothiophene H-Ftaa Attenuates The Toxicity Of Different A Beta Species

The prevailing opinion is that prefibrillar beta-amyloid (A beta) species, rather than end-stage amyloid fibrils, cause neuronal dysfunction in Alzheimer's disease, although the mechanisms behind A beta neurotoxicity remain to be elucidated. Luminescent conjugated oligothiophenes (LCOs) exhibit spectral properties upon binding to amyloid proteins and have previously been reported to change the toxicity of A beta(1- 42) and prion protein. In a previous study, we showed that an LCO, pentamer formyl thiophene acetic acid (p-FTAA), changed the toxicity of A beta(1-42). Here we investigated whether an LCO, heptamer formyl thiophene acetic acid (h-FTAA), could change the toxicity of A beta(1-42) by comparing its behavior with that of p-FTAA. Moreover, we investigated the effects on toxicity when A ss with the Arctic mutation (A beta Arc) was aggregated with both LCOs. Cell viability assays on SH-SY5Y neuroblastoma cells demonstrated that h-FTAA has a stronger impact on A beta(1-42) toxicity than does p-FTAA. Interestingly, h-FTAA, but not p-FTAA, rescued the A beta(Arc)-mediated toxicity. Aggregation kinetics and binding assay experiments with A beta(1-42) and A beta(Arc) when aggregated with both LCOs showed that h-FTAA and p-FTAA either interact with different species or affect the aggregation in different ways. In conclusion, h-FTAA protects against A beta(1-42) and A beta(Arc) toxicity, thus showing h-FTAA to be a useful tool for improving our understanding of the process of A beta aggregation linked to cytotoxicity.