(191bv) Engineering of a Protein Probe for Alpha-Synuclein Detection

Authors: 
Candreva, J., New York University
Chau, E., New York University
Kim, J. R., New York University
The aggregation of the amyloid, alpha-synuclein, has been implicated in the pathology of the neurodegenerative disorder, Parkinson’s Disease. Natively unstructured monomers of alpha-synuclein mis-fold and self-assemble to form prefibrillar oligomers, which are the most neurotoxic conformers. A system for the rapid and specific detection of these oligomeric intermediates would be beneficial towards uncovering the mechanism behind alpha-synuclein oligomerization, developing of therapeutic treatments, and the discovery of early diagnostic tools. Our group has developed a biomolecular probe, which retains the natural self-assembly of alpha-synuclein and incorporates a conformational fluorescence sensitivity to the biarsenical dye, FlAsH, in the presence of oligomers. A directed evolution approach was applied to optimize the probe and identify the best recombinant variants.