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)(2)dppz](2+) (phen =1,10-phenanthroline, dppz = dipyrido[3,2-a:2 '.3 '-c]phenazine), to study aggregation of alpha-synuclein (alpha S), which is associated with the development of Parkinson's disease. We demonstrated the use of [Ru(phen)(2)dppz](2+) to monitor alpha S fibril formation in real-time and to detect and quantify alpha S aggregates in neuroglioma cells, thereby providing a novel molecular tool to study protein deposition diseases in vitro and in vivo.