Uliassi Elisa, Bolognesi Maria Laura, Milelli Andrea
Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna, Via Belmeloro 6, Bologna 40126, Italy.
Department for Life Quality Studies, Alma Mater Studiorum - University of Bologna, Corso d'Augusto 237, Rimini 47921, Italy.
ACS Pharmacol Transl Sci. 2025 Feb 10;8(3):654-672. doi: 10.1021/acsptsci.4c00733. eCollection 2025 Mar 14.
Dysregulation of correct protein tau homeostasis represents the seed for the development of several devastating central nervous system disorders, known as tauopathies, that affect millions of people worldwide. Despite massive public and private support to research funding, these diseases still represent unmet medical needs. In fact, the tau-targeting tools developed to date have failed to translate into the clinic. Recently, taking advantage of the modes that nature uses to mediate the flow of information in cells, researchers have developed a new class of molecules, called proximity-inducing modulators, which exploit spatial proximity to modulate protein function(s) and redirect cellular processes. In this perspective, after a brief discussion about tau protein and the classic tau-targeting approaches, we will discuss the different classes of proximity-inducing modulators developed so far and highlight the applications to modulate tau protein's function and tau-induced toxicity.
正确的蛋白质tau稳态失调是几种毁灭性中枢神经系统疾病（即tau蛋白病）发展的根源，这些疾病影响着全球数百万人。尽管获得了大量公共和私人资金支持用于研究，但这些疾病仍存在未满足的医疗需求。事实上，迄今为止开发的靶向tau蛋白的工具未能转化为临床应用。最近，研究人员利用自然界中用于介导细胞内信息流的方式，开发了一类新的分子，称为邻近诱导调节剂，这类分子利用空间邻近性来调节蛋白质功能并重新引导细胞过程。从这个角度来看，在简要讨论tau蛋白和经典的靶向tau蛋白的方法之后，我们将讨论迄今为止开发的不同类别的邻近诱导调节剂，并强调其在调节tau蛋白功能和tau诱导的毒性方面的应用。
