Amplification of Tau fibrils from minute quantities of seeds.

Amplification of Tau fibrils from minute quantities of seeds.
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DOI:
10.1021/bi501050g
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发表时间:
2014-09-16
期刊:
影响因子:
2.9
通讯作者:
Margittai, Martin
Margittai, Martin
中科院分区:
生物学3区
文献类型:
--
作者:
Meyer, Virginia;Dinkel, Paul D.;Hager, Emily Rickman;Margittai, Martin

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阿尔茨海默病(AD)中Tau病理学的传播被认为是通过Tau蛋白模板化转化为原纤维和有延伸能力的种子的细胞到细胞转移进行的。为了研究Tau转化的效率,我们采用了用于朊病毒转化的蛋白质错误折叠循环扩增测定。利用肝素作为辅因子并采用剪切和生长的重复循环,合成的Tau原纤维和AD脑提取物中的Tau原纤维逐渐扩增。同时,自成核被抑制。结果强调了Tau原纤维的断裂诱导的复制作为疾病传播的潜在促进剂。
The propagation of Tau pathology in Alzheimer’s disease (AD) is thought to proceed through templated conversion of Tau protein into fibrils and cell-to-cell transfer of elongation-competent seeds. To investigate the efficiency of Tau conversion, we adapted the protein misfolding cyclic amplification assay used for the conversion of prions. Utilizing heparin as a cofactor and employing repetitive cycles of shearing and growth, synthetic Tau fibrils and Tau fibrils in AD brain extract are progressively amplified. Concurrently, self-nucleation is suppressed. The results highlight breakage-induced replication of Tau fibrils as a potential facilitator of disease spread.
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