title: Site-specific structural dynamics of α-Synuclein revealed by time-resolved fluorescence spectroscopy: a review.
abstract: Aggregation of α-Synuclein (α-Syn) into amyloid fibrils is known to be associated with the pathogenesis of Parkinson's disease (PD). Several missense mutations of the α-Syn gene have been associated with rare, early onset familial forms of PD. Despite several studies done so far, the local/residue-level structure and dynamics of α-Syn in its soluble and aggregated fibril form and how these are affected by the familial PD associated mutations are still not clearly understood. Here, we review studies performed by our group as well as other research groups, where time-resolved fluorescence spectroscopy has been used to understand the site-specific structure and dynamics of α-Syn under physiological conditions as well as under conditions that alter the aggregation properties of the protein such as low pH, high temperature, presence of membrane mimics and familial PD associated mutations. These studies have provided important insights into the critical structural properties of α-Syn that may govern its aggregation. The review also highlights time-resolved fluorescence as a promising tool to study the critical conformational transitions associated with early oligomerization of α-Syn, which are otherwise not accessible using other commonly used techniques such as thioflavin T (ThT) binding assay.
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400 076, India. Author to whom any correspondence should be addressed.
authors.forename: Shruti
authors.initials: S
authors.lastname: Sahay
authors.forename: G
authors.initials: G
authors.lastname: Krishnamoorthy
authors.forename: Samir K
authors.initials: SK
authors.lastname: Maji
mesh_terms: D000682:Amyloid; D006801:Humans; D020125:Mutation, Missense; D010300:Parkinson Disease; D013050:Spectrometry, Fluorescence; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D000682:Amyloid; D051844:alpha-Synuclein