α1-Antichymotrypsin interaction with Aβ(1–42) does not inhibit fibril formation but attenuates the peptide toxicity

Abstract

α1-Antichymotrypsin (ACT) is intimately associated with senile plaques in the Alzheimer's diseased (AD) brain. It was reported that ACT can promote the polimerization of Aβ(1–42) into amyloid filaments. It was suggested that neurotoxic amyloid deposits arise when β-peptide is induced to form fibrils by ACT or other amyloid-promoting factors (pathological chaperones) expressed in AD brain. However, it was reported recently that ACT can inhibit fibrillization of Aβ(1–40) and disaggregate pre-formed β-amyloid fibrils of this synthetic Aβ peptide. Our previous study [Aksenova et al., Neurosci. Lett., 411 (1996) 43–48] confirmed that ACT is able to inhibit Aβ(1–40) aggregation into fibrils, but it was shown that at the same time ACT does not change the peptide cytotoxicity. In this report we have observed that interaction of ACT with Aβ(1–42), unlike that for ACT-Aβ(1–40) interaction, does not prevent the formation of insoluble Aβ(1–42) aggregates, but completely blocks the peptide's toxicity in rat hippocampal cell cultures. These results are discussed in terms of the potential double role of peptide-protein interactions on Aβ aggregation and neurotoxicity.