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: Nathan P Cook, Kiri Kilpatrick, Laura Segatori, Angel A Martí
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 134 Issue 51 Pg. 20776-82 (Dec 26 2012) ISSN: 1520-5126 [Electronic] United States
• PMID: 23237404 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Amyloid
• Luminescent Agents
• Organometallic Compounds
• alpha-Synuclein
• ruthenium dipyridophenazine

Topics

• Amyloid (analysis)
• Cell Line, Tumor
• Humans
• Luminescent Agents (analysis)
• Microscopy, Fluorescence
• Organometallic Compounds (analysis)
• alpha-Synuclein (analysis)