Amyloid-β Peptide Induces Prion Protein Amyloid Formation: Evidence for Its Widespread Amyloidogenic Effect
Amyloid-β Peptide Induces Prion Protein Amyloid Formation: Evidence for Its Widespread Amyloidogenic Effect
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淀粉样蛋白-β 肽诱导朊病毒蛋白淀粉样蛋白形成：其广泛的淀粉样蛋白形成作用的证据
DOI：
10.1002/ange.201800197
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发表时间：
2018
影响因子：
--
通讯作者：
Honda Ryo
中科院分区：
文献类型：
--
作者：
Honda Ryo;Kuwata Kazuo;Honda Ryo
传染性海绵状脑病与朊病毒蛋白（PrP）错误折叠成富含淀粉样β蛋白的聚集体有关。以往的研究表明PrP与阿尔茨海默病淀粉样β肽（Aβ）相互作用，但这种相互作用如何影响PrP的错误折叠仍不清楚。这项研究首次提出了体外证据，表明Aβ在亚微摩尔浓度下诱导PrP-淀粉样蛋白形成。 有趣的是，PrP的系统性突变显示Aβ不需要PrP中的特定氨基酸序列，并且以类似于PrP的方式诱导其他不相关蛋白质（胰岛素和溶菌酶）错误折叠成淀粉样纤维。Aβ的这种非预期的非特异性淀粉样蛋白生成作用表明，无论靶蛋白的氨基酸序列如何，该肽可能参与广泛的蛋白质聚集，并加剧许多神经退行性疾病的病理。
Transmissible spongiform encephalopathy is associated with misfolding of prion protein (PrP) into an amyloid β‐rich aggregate. Previous studies have indicated that PrP interacts with Alzheimer′s disease amyloid‐β peptide (Aβ), but it remains elusive how this interaction impacts on the misfolding of PrP. This study presents the first in vitro evidence that Aβ induces PrP‐amyloid formation at submicromolar concentrations. Interestingly, systematic mutagenesis of PrP revealed that Aβ requires no specific amino acid sequences in PrP, and induces the misfolding of other unrelated proteins (insulin and lysozyme) into amyloid fibrils in a manner analogous to PrP. This unanticipated nonspecific amyloidogenic effect of Aβ indicates that this peptide might be involved in widespread protein aggregation, regardless of the amino acid sequences of target proteins, and exacerbate the pathology of many neurodegenerative diseases.