当前位置:科学网首页 > 小柯机器人 >详情
科学家开发出一种用于治疗tau病的新型tau去磷酸化靶向嵌合体
作者:小柯机器人 发布时间:2024/7/5 16:03:16

华中科技大学王建枝等研究人员合作开发出一种用于治疗tau病的新型tau去磷酸化靶向嵌合体。这一研究成果于2024年7月2日在线发表在国际学术期刊《中国药理学报》上。

研究人员表示,高磷酸化tau蛋白的异常积累在包括阿尔茨海默病(AD)在内的一系列被称为tau病的神经退行性疾病中起着关键作用。研究人员最近构思设计了异质双功能嵌合体,用于选择性地促进tau和磷酸酶之间的接近,从而专门促进tau去磷酸化和清除。

研究人员试图优化tau去磷酸化靶向嵌合体(DEPTAC)的构建,并获得了一种新的嵌合体D14,它在细胞和tau病小鼠模型中都能高效地减少tau磷酸化,同时显示出有限的细胞毒性。此外,D14还能改善经毒性tau-K18片段处理的原代培养海马神经元的神经退行性变,并改善tau病小鼠的认知功能。
 
这些结果表明,D14是治疗tau病的一种经济有效的候选药物。
 
附:英文原文

Title: A new tau dephosphorylation-targeting chimera for the treatment of tauopathies

Author: Su, Jing-fen, Xiao, Yue, Wei, Lin-yu, Lei, Hui-yang, Sun, Fei, Wang, Wei-xia, Li, Shi-hong, Wang, Xiao-chuan, Zheng, Jie, Wang, Jian-zhi

Issue&Volume: 2024-07-02

Abstract: Abnormal accumulation of hyperphosphorylated tau protein plays a pivotal role in a collection of neurodegenerative diseases named tauopathies, including Alzheimer’s disease (AD). We have recently conceptualized the design of hetero-bifunctional chimeras for selectively promoting the proximity between tau and phosphatase, thus specifically facilitating tau dephosphorylation and removal. Here, we sought to optimize the construction of tau dephosphorylating-targeting chimera (DEPTAC) and obtained a new chimera D14, which had high efficiency in reducing tau phosphorylation both in cell and tauopathy mouse models, while showing limited cytotoxicity. Moreover, D14 ameliorated neurodegeneration in primary cultured hippocampal neurons treated with toxic tau-K18 fragments, and improved cognitive functions of tauopathy mice. These results suggested D14 as a cost-effective drug candidate for the treatment of tauopathies.

DOI: 10.1038/s41401-024-01326-4

Source: https://www.nature.com/articles/s41401-024-01326-4

期刊信息

Acta Pharmacologica Sinica《中国药理学报》,创刊于1980年。隶属于施普林格·自然出版集团,最新IF:8.2

官方网址:http://www.chinaphar.com/
投稿链接:https://mc.manuscriptcentral.com/aphs