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由酸化定义的人类陶病菌株在R1-R2重复域的tau的酸化

Ethan D Smith^1,2, Quan Vo^1,2, Benoit I Giasson^1,2,3

¹Center for Translational Research in Neurodegenerative Disease, University of Florida, 1275 Center Drive, BMS J484, Gainesville, FL, 32610, USA.

Acta neuropathologica communications

|October 27, 2023

概括

陶蛋白上的酸化模式影响其在陶病症中的播种. 在特定部位模仿酸化减少了阿尔茨海默病的tau播种,但没有渐进性超核麻的tau播种,揭示了疾病特异性的代码.

科学领域:

神经科学是一个神经科学.
生物化学生物化学
病理学病理学病理学

背景情况:

陶蛋白是陶病的核心,后翻译修饰 (PTMs) 定义了特定疾病的含有.
阿尔茨海默病 (AD) 和渐进性超核麻 (PSP) 是不同的病,具有不同的病理特征.

研究的目的:

研究TAU酸化在AD-tau和PSP-tau的模板TAU播种中的作用.
确定特定的酸化点是否决定了的播种效率和菌株形成.

主要方法:

从AD和PSP患者中使用了不溶于洗剂的.
在P301L结构中采用酸化剥离 (Ala) 和酸化模仿 (Glu) 突变.
使用AD-tau和PSP-tau种子评估了tau播种的有效性.
在关键表位 (AT8,AT100,AT180,PHF1) 上分析了tau的酸化状态.

主要成果:

酸化抑制突变没有改变播种效率.
在Ser262/Thr263/Ser289/Ser305的酸化模仿突变减少了AD-tau播种,但没有减少PSP-tau播种.
化模仿突变Ser305 (Ser305Glu) 特别废除了AD-tau播种.
突变的在多个表位上显示出缺乏酸化,这表明了域间的合作性.

结论:

酸化PTMs形成一个关键的代码,该代码控制tau播种.
氨酸305酸化是AD-tau特异性播种的关键决定因素.
独特的酸-PTM代码有助于在4R病症中形成疾病特异的菌株.

关键词:

阿尔茨海默氏症是阿尔茨海默氏症的一种疾病.后翻译修改后的修改.渐进性的超核性.播种播种播种播种

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