Abstract
The main pathological hallmark of a group of neurodegenerative diseases called tauopathies is the formation of intracellular aggregates composed of the tau protein in the brain. Despite promising results in preclinical studies, tau immunotherapies in clinical development for the treatment of tauopathies, including Alzheimer’s disease, have thus far failed to improve patient cognition. Owing to its critical pathological role, most still argue that tau is an excellent therapeutic target. Therefore, better understanding of the mechanisms by which tau antibodies can remove pathogenic tau from the brain and how these processes can be exploited is paramount for the design of second-generation immunotherapies. On page 1336 of this issue, Mukadam et al. show that the cytoplasmic antibody receptor and E3 ubiquitin ligase tripartite motif-containing 21 (TRIM21) is required for effective tau immunotherapy in a tauopathy mouse model, providing an area of focus for the development of future tau antibodies.
摘要
一组被称为tau蛋白病(tauopathies)的神经退行性疾病的主要病理特征是在大脑中形成由tau蛋白组成的细胞内聚集物。尽管在临床前研究中取得了可喜的成果，但用于治疗包括阿尔茨海默病在内的tau蛋白病的临床开发中的tau蛋白免疫疗法迄今未能改善患者的认知功能。由于其关键的病理作用，大多数人仍然认为tau是一个优秀的治疗靶点。因此，更好地了解tau抗体从大脑中清除致病性tau的机制以及如何利用这些过程，对于设计第二代免疫疗法至关重要。在本期的第1336页，Mukadam等的研究表明，在一个tauopathy小鼠模型中，细胞质抗体受体和E3泛素化连接酶TRI的开发提供了一个重点领域。
参考文献
Nisbet R. M. (2023). Effective immunotherapy occurs in neurons. Science (New York, N.Y.), 379(6639), 1300–1301. https://doi.org/10.1126/science.adg9800.
