Site-Specific Fluorescence Polarization For Studying The Disaggregation Of Alpha-Synuclein Fibrils By Small Molecules

Fibrillar aggregates of the protein alpha-synuclein (alpha S) are one of the hallmarks of Parkinson's disease. Here, we show that measuring the fluorescence polarization (FP) of labels at several sites on aS allows one to monitor changes in the local dynamics of the protein after binding to micelles or vesicles, and during fibril formation. Most significantly, these site-specific FP measurements provide insight into structural remodeling of aS fibrils by small molecules and have the potential for use in moderate-throughput screens to identify small molecules that could be used to treat Parkinson's disease.