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Prediction of fibril formation by early-stage amyloid peptide aggregation.
Journal of Pharmaceutical Analysis ( IF 6.1 ) Pub Date : 2019-12-13 , DOI: 10.1016/j.jpha.2019.12.002
Jiaojiao Hu 1, 2 , Huiyong Sun 2, 3 , Haiping Hao 2, 4 , Qiuling Zheng 1, 2
Affiliation  

Amyloid fibrils are found in systemic amyloidosis diseases such as Alzheimer’s disease, Parkinson’s disease, and type II diabetes. Currently, these diseases are diagnosed by observation of fibrils or plaques, which is an ineffective method for early diagnosis and treatment of disease. The goal of this study was to develop a simple and quick method to predict the possibility and speed of fibril formation before its occurrence. Oligomers generated from seven representative peptide segments were first isolated and detected by ion-mobility mass spectrometry (IM-MS). Then, their assemblies were disrupted using formic acid (FA). Interestingly, oligomers that showed small ion intensity changes upon FA addition had rapid fibril formation. By contrast, oligomers that had large ion intensity changes generated fibrils slowly. Two control peptides (aggregation/no fibrils and no aggregation/no fibrils) did not show changes in their ion intensities, which confirmed the ability of this method to predict amyloid formation. In summary, the developed method correlated MS intensity ratio changes of peptide oligomers on FA addition with their amyloid propensities. This method will be useful for monitoring peptide/protein aggregation behavior and essential for their mechanism studies.



中文翻译:

通过早期淀粉样蛋白肽聚集预测原纤维形成。

淀粉样蛋白原纤维存在于系统性淀粉样变性病中,例如阿尔茨海默氏病,帕金森氏病和II型糖尿病。当前,这些疾病是通过观察原纤维或斑块来诊断的,这对于疾病的早期诊断和治疗是无效的方法。这项研究的目的是开发一种简单快速的方法来预测原纤维形成之前的可能性和速度。首先分离由七个代表性肽段产生的寡聚体,并通过离子迁移质谱(IM-MS)检测。然后,使用甲酸(FA)破坏其组装。有趣的是,添加FA时离子强度变化较小的低聚物具有快速的原纤维形成。相反,具有大的离子强度变化的低聚物缓慢产生原纤维。两种对照肽(聚集/无原纤维和无聚集/无原纤维)的离子强度没有变化,这证实了该方法预测淀粉样蛋白形成的能力。总之,开发的方法将添加FA时的肽寡聚物的MS强度比变化与淀粉样蛋白倾向相关联。该方法对于监测肽/蛋白质聚集行为将是有用的,并且对于它们的机理研究是必不可少的。

更新日期:2019-12-13
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