【摘 要】
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Parkinsons disease and dementia with Lewy bodies are featured with the formation of Lewy bodies, composed mostly of α-Synuclein (α-Syn) in the brain.Although evidence indicates that the large oligomer
【机 构】
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Department of Physics, Pohang University of Science and Technology, Pohang, South Korea
【出 处】
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The 9th Asian Biophysics Association Symposium (ABA2015)(第九届
论文部分内容阅读
Parkinsons disease and dementia with Lewy bodies are featured with the formation of Lewy bodies, composed mostly of α-Synuclein (α-Syn) in the brain.Although evidence indicates that the large oligomeric or protofibril forms of α-Syn are neurotoxic agents, the detailed mechanisms of the toxic functions of the oligomers remain unclear.Here we present new single-vesicle fusion assay using alternating laser excitation.Using this method, we discriminate fused vesicles from docked vesicles without surface immobilization.Then, we show that large α-Syn oligomers efficiently inhibit neuronal SNARE-mediated vesicle lipid mixing by using single-vesicle assay.Large α-Syn oligomers preferentially bind to the N-terminal domain of a vesicular SNARE protein synaptobrevin-2, which blocks SNARE-mediated lipid mixing by preventing SNARE complex formation.In sharp contrast, the α-Syn monomer has a negligible effect on lipid mixing even with a 30-fold excess compared with the case of large α-Syn oligomers.Thus, the results suggest that large α-Syn oligomers function as inhibitors of dopamine release, which provides a clue, at the molecular level, to their neurotoxicity.Finally, we develop new chemical FRET probes for observing content mixing, which have better properties than DNA hairpin.
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