%0 Journal Article
%T Conformational-Switch Based Strategy Triggered by [18] ¦Ð Heteroannulenes toward Reduction of Alpha Synuclein Oligomer Toxicity
%J -
%D 2019
%R https://doi.org/10.1021/acschemneuro.8b00436
%X A water-soluble meso-carboxy aryl substituted [18] heteroannulene (porphyrin) and its Zn-complex have been found to be viable in targeting ¦Á-Syn aggregation at all its key microevents, namely, primary nucleation, fibril elongation, and secondary nucleation, by converting the highly heterogeneous and cytotoxic aggresome into a homogeneous population of minimally toxic off-pathway oligomers, that remained unexplored until recently. With the EC50 and dissociation constants in the low micromolar range, these heteroannulenes induce a switch in the secondary structure of toxic prefibrillar on-pathway oligomers of ¦Á-Syn, converting them into minimally toxic nonseeding off-pathway oligomers. The inhibition of the aggregation and the reduction of toxicity have been studied in vitro as well as inside neuroblastoma cells
%U https://pubs.acs.org/doi/10.1021/acschemneuro.8b00436