posted on 2012-12-26, 00:00authored byNathan
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.