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

Article

Abstract

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.

Keywords

Single-molecule fluorescence Aggregation Amyloid Oligomers Parkinson’s disease 

Abbreviations

AS

α-Synuclein

PD

Parkinson’s disease

NAC

Nonamyloid beta component

FRET

Förster resonance energy transfer

SDS

Sodium dodecyl sulfate

CMC

Critical micelle concentration

CD

Circular dichroism

LUV

Large unilamellar vesicle

FCS

Fluorescence correlation spectroscopy

FIDA

Fluorescence intensity distribution analysis

SIFT

Scanning for intensely fluorescent targets

FCCS

Fluorescence cross-correlation spectroscopy

FKBP

FK506 binding protein

MMP

Matrix metalloprotease

NBB

N′-benzylidene-benzohydrazide

ETeff

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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