Fluorescent Probe for Selective Imaging of α-Synuclein Fibrils in Living Cells.

Pankaj Gaur, Maksym Galkin, Andrii Kurochka, Subrata Ghosh, Dmytro A Yushchenko, Volodymyr V Shvadchak

ACS chemical neuroscience 2021 Apr 21

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Plaques of amyloid fibrils composed of neuronal protein α-synuclein are one of the hallmarks of Parkinson's disease, and their selective imaging is crucial to study the mechanism of its pathogenesis. However, the existing fluorescent probes for amyloids are efficient only in solution and tissue systems, and they are not selective enough for the visualization of amyloid fibrils in living cells. In this study, we present two molecular rotor-based probes RB1 and RB2. These thiazolium probes show affinity to α-synuclein fibrils and turn-on fluorescence response upon interactions. Because of its extended π-conjugation and high rotational degree of freedom, RB1 exhibits a 76 nm red-shift of absorption maxima and 112-fold fluorescence enhancement upon binding to amyloid fibrils. Owing to its strong binding affinity to α-synuclein fibrils, RB1 can selectively stain them in the cytoplasm of living HeLa and SH-SY5Y cells with high optical contrast. RB1 is a cell-permeable and noncytotoxic probe. Taken together, we have demonstrated that RB1 is an amyloid probe with an outstanding absorption red-shift that can be used for intracellular imaging of α-synuclein fibrils.

Citation

Pankaj Gaur, Maksym Galkin, Andrii Kurochka, Subrata Ghosh, Dmytro A Yushchenko, Volodymyr V Shvadchak. Fluorescent Probe for Selective Imaging of α-Synuclein Fibrils in Living Cells. ACS chemical neuroscience. 2021 Apr 21;12(8):1293-1298