Large α-synuclein oligomers inhibit neuronal SNARE-mediated vesicle docking

Choi B.-K.; Choi M.-G.; Kim J.-Y.Yang Y.Lai Y.Kweon D.-H.Lee N.K.Shin Y.-K.

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Large α-synuclein oligomers inhibit neuronal SNARE-mediated vesicle docking

机译：Large α-synuclein oligomers inhibit neuronal SNARE-mediated vesicle docking

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Parkinson disease and dementia with Lewybodies 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, weshowthat large α-Syn oligomers efficiently inhibit neuronal SNARE-mediated vesicle lipid mixing. 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 thus provides a clue, at the molecular level, to their neurotoxicity.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2013年第10期|4087-4092|共6页
作者
Choi B.-K.; Choi M.-G.; Kim J.-Y.Yang Y.Lai Y.Kweon D.-H.Lee N.K.Shin Y.-K.;
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作者单位

School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 790-784, South Korea;

Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, South Korea;

Department of Physics, Pohang University of Science and Technology, Pohang 790-784, South KoreaDepartment of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, IA 50011, United StatesDepartment of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon 440-746, South Korea;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Alternating-laser excitation; Exocytosis; Neuroscience; Single-vesicle; Vesicle fusion;

Large α-synuclein oligomers inhibit neuronal SNARE-mediated vesicle docking

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