HSP70 chaperones, J-domain proteins (JDPs) and nucleotide exchange factors (NEF) form functional networks that have the ability to prevent and reverse the aggregation of proteins associated with neurodegenerative diseases. JDPs can interact with specific substrate proteins, hold them in a refolding-competent conformation and target them to specific HSP70 chaperones for remodeling. Thereby, JDPs select specific substrates and constitute an attractive target for pharmacological intervention of neurodegenerative diseases. This, under the condition that the exact mechanism of JDPs interaction with specific substrates is unveiled. In this review, we provide an overview of the structural and functional variety of JDPs that interact with neurodegenerative disease-associated proteins and we highlight those studies that identified specific residues, domains or regions of JDPs that are crucial for substrate binding.

HSP70伴侣，J结构域蛋白（JDP）和核苷酸交换因子（NEF）形成功能性网络，这些功能性网络具有预防和逆转与神经退行性疾病相关的蛋白质聚集的能力。JDP可以与特定的底物蛋白相互作用，将它们保持在具有折叠功能的构象中，并将它们靶向特定的HSP70伴侣进行重塑。因此，JDP选择特定的底物，并构成神经退行性疾病的药理干预的有吸引力的目标。在揭示JDP与特定底物相互作用的确切机理的条件下。在这篇综述中，我们概述了与神经退行性疾病相关蛋白相互作用的JDP的结构和功能，并重点介绍了鉴定特定残基的研究，