Institute of Enzymology, Research Centre for Natural Sciences, ELKH, 1117 Budapest, Hungary.
Laboratory of Microbiology Signals and Microenvironment, University of Rouen, 76821 Mont Saint Aignan, France.
Int J Mol Sci. 2022 Jan 28;23(3):1550. doi: 10.3390/ijms23031550.
Protein-protein interactions (PPIs) outnumber proteins and are crucial to many fundamental processes; in consequence, PPIs are associated with several pathological conditions including neurodegeneration and modulating them by drugs constitutes a potentially major class of therapy. Classically, however, the discovery of small molecules for use as drugs entails targeting individual proteins rather than targeting PPIs. This is largely because discovering small molecules to modulate PPIs has been seen as extremely challenging. Here, we review the difficulties and limitations of strategies to discover drugs that target PPIs directly or indirectly, taking as examples the disordered proteins involved in neurodegenerative diseases.
蛋白质-蛋白质相互作用 (PPIs) 的数量超过了蛋白质，并且对许多基本过程至关重要；因此，PPIs 与几种病理状况有关，包括神经退行性变，通过药物调节它们构成了一类潜在的主要治疗方法。然而，传统上，发现用于药物的小分子需要针对单个蛋白质，而不是针对 PPI。这在很大程度上是因为发现调节 PPI 的小分子被认为极具挑战性。在这里，我们以涉及神经退行性疾病的无序蛋白质为例，综述了直接或间接发现靶向 PPI 的药物的策略的困难和局限性。
