@misc{10481/62603,
year = {2012},
month = {5},
url = {http://hdl.handle.net/10481/62603},
abstract = {Here, we use single-molecule techniques to study
the aggregation of α-synuclein, the protein whose
misfolding and deposition is associated with Parkinson’s disease. We identify a conformational change
from the initially formed oligomers to stable, more
compact proteinase-K-resistant oligomers as the
key step that leads ultimately to fibril formation.
The oligomers formed as a result of the structural
conversion generate much higher levels of oxidative
stress in rat primary neurons than do the oligomers
formed initially, showing that they are more
damaging to cells. The structural conversion is
remarkably slow, indicating a high kinetic barrier for
the conversion and suggesting that there is a significant period of time for the cellular protective
machinery to operate and potentially for therapeutic
intervention, prior to the onset of cellular damage. In
the absence of added soluble protein, the assembly
process is reversed and fibrils disaggregate to form
stable oligomers, hence acting as a source of cytotoxic species.},
organization = {Human Frontier Science Program
	
LT000795/2009},
organization = {Schiff Foundation},
organization = {European Union (EU)},
organization = {Gates Cambridge Scholarship},
organization = {FEBS Fellowship},
organization = {Italian Ministry of Education},
organization = {University and Research},
organization = {Wellcome/MRC Parkinson's Disease Consortium},
organization = {University of Sheffield},
organization = {MRC Protein Phosphorylation Unit at the University of Dundee 	
WT089698},
organization = {Augustus Newman Foundation},
organization = {Wellcome Trust},
organization = {Leverhulme Trust},
organization = {Medical Research Council UK (MRC)},
organization = {Engineering & Physical Sciences Research Council (EPSRC)},
organization = {Biotechnology and Biological Sciences Research Council (BBSRC)
	
BB/E019927/1},
organization = {European Commission Joint Research Centre
	
LSHM-CT-2006-037525},
organization = {Biotechnology and Biological Sciences Research Council (BBSRC)
	
BB/E019927/1},
organization = {Medical Research Council UK (MRC)
	
MC_G1000734
MC_G1000735},
publisher = {Elsevier},
title = {Direct Observation of the Interconversion of Normal and Toxic Forms of α-Synuclein},
doi = {10.1016/j.cell.2012.03.037},
author = {Cremades, Nunilo and Orte Gutiérrez, Ángel},
}