posted on 2021-09-01, 16:40authored byLinnea Sandin, Simon Sjödin, Ann-Christin Brorsson, Katarina Kågedal, Livia Civitelli
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) exhibit spectral properties upon binding to amyloid proteins
and have previously been reported to change the toxicity of Aβ1–42 and prion protein. In a previous study, we showed
that an LCO, pentamer formyl thiophene acetic acid (p-FTAA), changed
the toxicity of Aβ1–42. Here we investigated
whether an LCO, heptamer formyl thiophene acetic acid (h-FTAA), could
change the toxicity of Aβ1–42 by comparing
its behavior with that of p-FTAA. Moreover, we investigated the effects
on toxicity when Aβ with the Arctic mutation (AβArc) was aggregated with both LCOs. Cell viability assays on SH-SY5Y
neuroblastoma cells demonstrated that h-FTAA has a stronger impact
on Aβ1–42 toxicity than does p-FTAA. Interestingly,
h-FTAA, but not p-FTAA, rescued the AβArc-mediated
toxicity. Aggregation kinetics and binding assay experiments with
Aβ1–42 and AβArc 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 Aβ1–42 and AβArc toxicity, thus showing h-FTAA to be a
useful tool for improving our understanding of the process of Aβ
aggregation linked to cytotoxicity.