Trehalose inhibits fibrillation of A53T mutant alpha-synuclein and disaggregates existing fibrils.
Trehalose inhibits fibrillation of A53T mutant alpha-synuclein and disaggregates existing fibrils.
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DOI：
10.1016/j.abb.2012.04.021
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发表时间：
2012-07
影响因子：
3.9
通讯作者：
Wen-Bo Yu;Teng Jiang;Danmei Lan;Jiahong Lu;Zhen-yu Yue;Jian Wang;P. Zhou
中科院分区：
文献类型：
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作者：
Wen-Bo Yu;Teng Jiang;Danmei Lan;Jiahong Lu;Zhen-yu Yue;Jian Wang;P. Zhou
α -突触核蛋白（AS）的聚集与帕金森病（PD）的发展有关键关系，抑制这一过程可能有效治疗PD。这里，我们通过圆二色光谱、硫黄素T荧光、原子力显微镜等手段发现，低浓度海藻糖使预形成的A53T AS原原纤维和原纤维分解成小聚集体甚至无序的线圈结构，而高浓度海藻糖则减缓了结构向β-片结构的转变，完全阻止了成熟A53T AS原纤维的形成。需要进一步的体内工作来评估其作为治疗帕金森病的新策略的潜力。
The aggregation of alpha-synuclein (AS) is pivotally implicated in the development of Parkinson’s disease (PD), inhibiting this process might be effective in treating PD. Here, by using circular dichroism spectroscopy, thioflavin T fluorescence, and atomic force microscopy, we found that trehalose at low concentration disaggregates preformed A53T AS protofibrils and fibrils into small aggregates or even random coil structure, while trehalose at high concentration slows down the structural transition into β-sheet structure and completely prevents the formation of mature A53T AS fibrils. Further work in vivo will be needed to evaluate its potential as a novel strategy for treating PD.