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Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2010

Open Access 01-12-2010 | Research article

α-synuclein induced synapse damage is enhanced by amyloid-β1-42

Authors: Clive Bate, Steve Gentleman, Alun Williams

Published in: Molecular Neurodegeneration | Issue 1/2010

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Abstract

Background

The pathogenesis of Parkinson's disease (PD) and dementia with Lewy bodies (DLB) is associated with the accumulation of aggregated forms of the α-synuclein (αSN) protein. An early event in the neuropathology of PD and DLB is the loss of synapses and a corresponding reduction in the level of synaptic proteins. However, the molecular mechanisms involved in synapse damage in these diseases are poorly understood. In this study the process of synapse damage was investigated by measuring the amount of synaptophysin, a pre-synaptic membrane protein essential for neurotransmission, in cultured neurons incubated with αSN, or with amyloid-β (Aβ) peptides that are thought to trigger synapse degeneration in Alzheimer's disease.

Results

We report that the addition of recombinant human αSN reduced the amount of synaptophysin in cultured cortical and hippocampal neurons indicative of synapse damage. αSN also reduced synaptic vesicle recycling, as measured by the uptake of the fluorescent dye FM1-43. These effects of αSN on synapses were modified by interactions with other proteins. Thus, the addition of βSN reduced the effects of αSN on synapses. In contrast, the addition of amyloid-β (Aβ)1-42 exacerbated the effects of αSN on synaptic vesicle recycling and synapse damage. Similarly, the addition of αSN increased synapse damage induced by Aβ1-42. However, this effect of αSN was selective as it did not affect synapse damage induced by the prion-derived peptide PrP82-146.

Conclusions

These results are consistent with the hypothesis that oligomers of αSN trigger synapse damage in the brains of Parkinson's disease patients. Moreover, they suggest that the effect of αSN on synapses may be influenced by interactions with other peptides produced within the brain.
Appendix
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Metadata
Title
α-synuclein induced synapse damage is enhanced by amyloid-β1-42
Authors
Clive Bate
Steve Gentleman
Alun Williams
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2010
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/1750-1326-5-55

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