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Cell:患者Tau蛋白修饰图谱可以识别阿尔兹海默症分期 

2020-11-14 haibei MedSci原创

最近,为了阐明Tau亚型和翻译后修饰(PTM)的计量学在阿尔茨海默病(AD)中的作用,研究人员从49名AD和42名对照组受试者的死后人类组织中分离出了Tau的多种亚型

已有的研究显示,阿尔兹海默症患者脑内具有大量病理性Tau蛋白的聚积。Tau蛋白聚积被认为参与了阿尔兹海默症的发生和进展。针对病理性Tau进行清除的方法有希望成为阿尔兹海默症患者的新型治疗手段。

最近,为了阐明Tau亚型和翻译后修饰(PTM)的计量学在阿尔茨海默病(AD)中的作用,研究人员从49名AD和42名对照组受试者的死后人类组织中分离出了Tau的多种亚型,并研究了这些亚型上面的95个翻译后修饰(PTM)的高分辨率定量蛋白质组学图。

虽然Tau PTM图揭示了不同受试者的异质性,但有一个PTM子集显示出AD的高占有率和频率,表明其在疾病中的重要性。

无监督分析表明,PTMs以有序方式发生,导致Tau聚集。通过对大小分化的Tau的分析,研究人员进一步确定了与tau传播相关的PTMs的过程性添加和最小集合。

综上所述,该研究确定了Tau蛋白在疾病不同阶段对疾病干预至关重要的特征,包括0N和4R异构体的富集,C端代表性不足,富脯氨酸区(PRR)负电荷增加,微管结合域(MBD)正电荷减少。

 

原始出处:

Hendrik Wesseling et al. Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease. Cell (2020). DOI:https://doi.org/10.1016/j.cell.2020.10.029

 

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    2021-01-10 维他命
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    2020-11-16 hb2008ye
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    2020-11-14 ms5000000905177585

    很不错

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