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针对一种依赖于形状的表位体的抗陶抗体可以选择性地结合种子

Brian D Hitt¹, Ankit Gupta², Ruhar Singh²

¹Center for Alzheimer's and Neurodegenerative Diseases, UT Southwestern Medical Center, Dallas, Texas, USA; Department of Neurology, UT Southwestern Medical Center, Dallas, Texas, USA; Department of Neurology, University of California, Irvine, California, USA.

The Journal of biological chemistry

|September 15, 2023

概括

新的抗体针对阿尔茨海默氏症和PSP等神经退行性疾病中的有毒tau种子. 这些抗体特异地与tau的转林形式结合,表明其在疾病发病过程中的作用以及诊断和治疗的潜力.

科学领域:

神经科学是一个神经科学.
生物化学生物化学
免疫学免疫学免疫学

背景情况:

神经退行性病,包括阿尔茨海默氏症 (AD),渐进性上核性 (PSP),皮质细胞底性退化 (CBD) 和皮克病 (PiD),是蛋白聚集的结果.
一个拟议的模型表明,单体存在于惰性 (Mi) 或种子竞争性 (Ms) 形式,在proline 301 (P301) 中的cis/trans异构化可能导致过渡到Ms状态.

研究的目的:

开发单克隆抗体,向的种子竞争形式.
调查P301处的转烯构成在陶聚合和神经退行性疾病的发病过程中的作用.

主要方法:

在重复1 (R1) 中,使用非天然抗原与化 (P*) 在270 (P270) 中产生单克隆抗体,偏向转化配置.
测试可溶性种子和来自各种病症和对照患者的大脑组织的免疫沉降和免疫染色的抗体疗效.

主要成果:

两种抗体,MD2.2和MD3.1,特别是来自AD和PSP脑样本的免疫沉积溶性种子,但不是来自CBD或PiD样本.
这些抗体有效地染色了AD,PSP和PiD患者的脑组织,但不是CBD或对照大脑,突出显示了trans-proline表位在特定陶氏病变中的相关性.
这些发现表明,在病原发生过程中,P301周围的局部展开.

结论:

强大的抗种子抗体已经产生,准了跨林表位.
结果表明,P301的转蛋白构造对特定神经退行性疾病中tau的播种和聚合至关重要.
MD2.2和MD3.1抗体显示出作为病的诊断和治疗工具的希望.

关键词:

氨基化物氨基化物形状的变化形状的变化形状特异性抗体的抗体是特定于形状的.普里昂是什么意思?普里昂是什么意思?知道的知道的知道的跨-氨酸-氨酸是什么

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