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在小鼠模型中有效的tau免疫疗法需要细胞质抗体受体TRIM21

Aamir S Mukadam^1,2, Lauren V C Miller^1,2, Annabel E Smith^1,2

¹UK Dementia Research Institute at the University of Cambridge, Cambridge CB2 0AH, UK.

Science (New York, N.Y.)

|March 30, 2023

概括

针对tau病理的抗体通过细胞质受体TRIM21 (T21) 有效. 这种机制通过防止神经元中的tau聚合来防止神经退行性疾病的进展.

科学领域:

神经科学
免疫学
蛋白质生物化学

背景情况:

蛋白聚合物与神经退行性疾病的发病有关.
抗体 (Ab) 疗法是有前途的,但它们的保护机制尚不清楚.

研究的目的:

研究细胞质抗体受体TRIM21 (T21) 在抗体介导的抗陶病态保护中的作用.
在神经退行性疾病模型中阐明抗体保护的细胞机制.

主要方法:

利用各种细胞和动物模型研究病理.
研究了抗体复合体与TRIM21受体的相互作用.
在T21缺陷模型中对tau聚合进行了评估.

主要成果:

抗体复合物被内化到神经细胞质中,引入TRIM21.
通过TRIM21的接触来防止种子聚.
TRIM21的丢失取消了对tau病理的抗体介导保护.

结论:

通过TRIM21,细胞是基于抗体的神经保护的关键部位.
这一发现为设计针对神经退行性疾病的新型抗体免疫疗法提供了洞察力.

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