Function and Dysfunction of α-Synuclein: Probing Conformational Changes and Aggregation by Single Molecule Fluorescence

The aggregation and deposition of the neuronal protein alpha-synuclein in the substantia nigra region of the brain is a key pathological feature of Parkinson's disease. alpha-Synuclein assembles from a monomeric state in solution, which lacks stable secondary and tertiary contacts, into highly structured fibrillar aggregates through a pathway which involves the population of multiple oligomeric species over a range of time scales. These features make alpha-synuclein well suited for study with single-molecule techniques, which are particularly useful for characterizing dynamic, heterogeneous samples. Here, we review the current literature featuring single-molecule fluorescence studies of alpha-synuclein and discuss how these studies have contributed to our understanding of both its function and its role in disease.