Molecular Neurobiology

, Volume 47, Issue 2, pp 622–631 | Cite as

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



The aggregation and deposition of the neuronal protein α-synuclein in the substantia nigra region of the brain is a key pathological feature of Parkinson’s disease. α-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 α-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 α-synuclein and discuss how these studies have contributed to our understanding of both its function and its role in disease.


Single-molecule fluorescence Aggregation Amyloid Oligomers Parkinson’s disease 





Parkinson’s disease


Nonamyloid beta component


Förster resonance energy transfer


Sodium dodecyl sulfate


Critical micelle concentration


Circular dichroism


Large unilamellar vesicle


Fluorescence correlation spectroscopy


Fluorescence intensity distribution analysis


Scanning for intensely fluorescent targets


Fluorescence cross-correlation spectroscopy


FK506 binding protein


Matrix metalloprotease




Energy transfer efficiency


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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Molecular Biophysics and BiochemistryYale UniversityNew HavenUSA

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