title: Detection of α-synuclein amyloidogenic aggregates in vitro and in cells using light-switching dipyridophenazine ruthenium(II) complexes.
abstract: 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 α-synuclein (αS), which is associated with the development of Parkinson's disease. We demonstrated the use of [Ru(phen)(2)dppz](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.
authors.affiliation: Department of Chemistry, Rice University, Houston, Texas 77005, USA.
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Cook
authors.forename: Kiri
authors.initials: K
authors.lastname: Kilpatrick
authors.forename: Laura
authors.initials: L
authors.lastname: Segatori
authors.forename: Angel A
authors.initials: AA
authors.lastname: Martí
mesh_terms: D000682:Amyloid / Q000032:analysis*; D045744:Cell Line, Tumor; D006801:Humans; D049408:Luminescent Agents / Q000032:analysis*; D008856:Microscopy, Fluorescence; D009942:Organometallic Compounds / Q000032:analysis*; D051844:alpha-Synuclein / Q000032:analysis*
chemical_list: D000682:Amyloid; D049408:Luminescent Agents; D009942:Organometallic Compounds; D051844:alpha-Synuclein; C483523:ruthenium dipyridophenazine