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Detection of α‑Synuclein Amyloidogenic Aggregates in Vitro and in Cells using Light-Switching Dipyridophenazine Ruthenium(II) Complexes

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journal contribution
posted on 26.12.2012, 00:00 authored by Nathan P. Cook, Kiri Kilpatrick, Laura Segatori, Angel A. Martí
Protein aggregation is the hallmark of a number of neurodegenerative diseases including Parkinson’s and Huntington’s diseases. There is a significant interest in understanding the molecular mechanisms involved in the self-association and fibrillization of monomeric soluble proteins into insoluble deposits in vivo and in vitro. Probes with novel properties, such as red-shifted emission, large Stokes shifts, and high photostability, are desirable for a variety of protein aggregation studies. To respond to the increasing need for aggregation–responsive compounds suitable to cellular studies, we present a ruthenium­(II) dipyridophenazine derivative, [Ru­(phen)2dppz]2+ (phen =1,10-phenanthroline, dppz = dipyrido­[3,2-a:2′.3′-c]­phenazine), to study aggregation of α-synuclein (αS), which is associated with the development of Parkinson’s disease. We demonstrated the use of [Ru­(phen)2dppz]2+ to monitor αS fibril formation in real-time and to detect and quantify αS aggregates in neuroglioma cells, thereby providing a novel molecular tool to study protein deposition diseases in vitro and in vivo.

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