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Biochim Biophys Acta. 2015 Aug;1852(8):1658-64. doi: 10.1016/j.bbadis.2015.05.002. Epub 2015 May 8.

Dimerization propensities of Synucleins are not predictive for Synuclein aggregation.

Author information

1
Department of Neurology, University Medical Center Goettingen, Waldweg 33, 37073 Goettingen, Germany; Cluster of Excellence, Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Goettingen, Germany. Electronic address: keckerm@gwdg.de.
2
Department of Neurology, University Medical Center Goettingen, Waldweg 33, 37073 Goettingen, Germany; Cluster of Excellence, Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Goettingen, Germany.

Abstract

Aggregation and fibril formation of human alpha-Synuclein (αS) are neuropathological hallmarks of Parkinson's disease and other synucleinopathies. The molecular mechanisms of αS aggregation and fibrillogenesis are largely unknown. Several studies suggested a sequence of events from αS dimerization via oligomerization and pre-fibrillar aggregation to αS fibril formation. In contrast to αS, little evidence suggests that γS can form protein aggregates in the brain, and for βS its neurotoxic properties and aggregation propensities are controversially discussed. These apparent differences in aggregation behavior prompted us to investigate the first step in Synuclein aggregation, i.e. the formation of dimers or oligomers, by Bimolecular Fluorescence Complementation in cells. This assay showed some Synuclein-specific limitations, questioning its performance on a single cell level. Nevertheless, we unequivocally demonstrate that all Synucleins can interact with each other in a very similar way. Given the divergent aggregation properties of the three Synucleins this suggests that formation of dimers is not predictive for the aggregation of αS, βS or γS in the aged or diseased brain.

KEYWORDS:

Aggregation; Bimolecular fluorescence complementation; Dimerization; Synuclein

PMID:
25960149
DOI:
10.1016/j.bbadis.2015.05.002
[Indexed for MEDLINE]
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