Title: Noninvasive bioluminescence imaging of α-synuclein oligomerization in mouse brain using split firefly luciferase reporters
Authors: Aelvoet, Sarah-Ann ×
Ibrahimi, Abdelilah
Macchi, Francesca
Gijsbers, Rik
Van Den Haute, Chris
Debyser, Zeger
Baekelandt, Veerle #
Issue Date: Dec-2014
Publisher: The Society for Neuroscience
Series Title: Journal of Neuroscience vol:34 issue:49 pages:16518-16532
Article number: 10.1523/JNEUROSCI.4933-13.2014
Abstract: Alpha-synuclein (αSYN) aggregation plays a pivotal role in the pathogenesis of Parkinson's disease and other synucleinopathies. In this multistep process, oligomerization of αSYN monomers is the first step in the formation of fibrils and intracytoplasmic inclusions. Although αSYN oligomers are generally considered to be the culprit of these diseases, the methodology currently available to follow-up oligomerization in cells and in brain is inadequate. We developed a split firefly luciferase complementation system to visualize oligomerization of viral vector-encoded αSYN fusion proteins. αSYN oligomerization resulted in successful luciferase complementation in cell culture and in mouse brain. Oligomerization of αSYN was monitored noninvasively with bioluminescence imaging in the mouse striatum and substantia nigra up to 8 months after injection. Moreover, the visualized αSYN oligomers retained their toxic and aggregation properties in both model systems. Next, the effect of two small molecules, FK506 and (-)-epigallocatechin-3-gallate (EGCG), known to inhibit αSYN fibril formation, was investigated. FK506 inhibited the observed αSYN oligomerization both in cell culture and in mouse brain. In conclusion, the split firefly luciferase-αSYN complementation assay will increase our insight in the role of αSYN oligomers in synucleinopathies and opens new opportunities to evaluate potential αSYN-based neuroprotective therapies.
ISSN: 0270-6474
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Virology and Gene Therapy
Research Group for Neurobiology and Gene Therapy
× corresponding author
# (joint) last author

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