RETRACTED: β-Amyloid and α-Synuclein Cooperate To Block SNARE-Dependent Vesicle Fusion(Retracted article. See vol. 56, pg.1026,2017)

被引:20
作者
Choi, Bong-Kyu [1 ]
Kim, Jae-Yeol [2 ]
Cha, Moon-Yong [3 ]
Mook-Jung, Inhee [3 ]
Shin, Yeon-Kyun [4 ]
Lee, Nam Ki [1 ,2 ]
机构
[1] Pohang Univ Sci & Technol, Sch Interdisciplinary Biosci & Bioengn, Pohang 790784, South Korea
[2] Pohang Univ Sci & Technol, Dept Phys, Pohang 790784, South Korea
[3] Seoul Natl Univ, Coll Med, Dept Biochem & Biomed Sci, Seoul 110799, South Korea
[4] Iowa State Univ, Dept Biochem Biophys & Mol Biol, Ames, IA 50011 USA
基金
美国国家卫生研究院; 新加坡国家研究基金会;
关键词
LEWY BODY PATHOLOGY; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; A-BETA; PRECURSOR PROTEIN; OLIGOMERS; DOPAMINE; MECHANISMS; DEMENTIA; LINK;
D O I
10.1021/acs.biochem.5b00087
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Alzheimers disease (AD) and Parkinsons disease (PD) are caused by beta-amyloid (A beta) and a-synuclein (alpha S), respectively. Ample evidence suggests that these two pathogenic proteins are closely linked and have a synergistic effect on eliciting neurodegenerative disorders. However, the pathophysiological consequences of A beta and alpha S coexistence are still elusive. Here, we show that large-sized alpha S oligomers, which are normally difficult to form, are readily generated by A beta(42)-seeding and that these oligomers efficiently hamper neuronal SNARE-mediated vesicle fusion. The direct binding of the A beta-seeded alpha S oligomers to the N-terminal domain of synaptobrevin-2, a vesicular SNARE protein, is responsible for the inhibition of fusion. In contrast, large-sized A beta(42) oligomers (or aggregates) or the products of alpha S incubated without A beta(42) have no effect on vesicle fusion. These results are confirmed by examining PC12 cell exocytosis. Our results suggest that A beta and alpha S cooperate to escalate the production of toxic oligomers, whose main toxicity is the inhibition of vesicle fusion and consequently prompts synaptic dysfunction.
引用
收藏
页码:1831 / 1840
页数:10
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