| First Author | Aelvoet SA | Year | 2014 |
| Journal | J Neurosci | Volume | 34 |
| Issue | 49 | Pages | 16518-32 |
| PubMed ID | 25471588 | Mgi Jnum | J:218741 |
| Mgi Id | MGI:5618340 | Doi | 10.1523/JNEUROSCI.4933-13.2014 |
| Citation | Aelvoet SA, et al. (2014) Noninvasive bioluminescence imaging of alpha-synuclein oligomerization in mouse brain using split firefly luciferase reporters. J Neurosci 34(49):16518-32 |
| abstractText | Alpha-synuclein (alphaSYN) aggregation plays a pivotal role in the pathogenesis of Parkinson's disease and other synucleinopathies. In this multistep process, oligomerization of alphaSYN monomers is the first step in the formation of fibrils and intracytoplasmic inclusions. Although alphaSYN 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 alphaSYN fusion proteins. alphaSYN oligomerization resulted in successful luciferase complementation in cell culture and in mouse brain. Oligomerization of alphaSYN was monitored noninvasively with bioluminescence imaging in the mouse striatum and substantia nigra up to 8 months after injection. Moreover, the visualized alphaSYN 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 alphaSYN fibril formation, was investigated. FK506 inhibited the observed alphaSYN oligomerization both in cell culture and in mouse brain. In conclusion, the split firefly luciferase-alphaSYN complementation assay will increase our insight in the role of alphaSYN oligomers in synucleinopathies and opens new opportunities to evaluate potential alphaSYN-based neuroprotective therapies. |
