Neurodegenerative disorders are invariably associated with intra- or extra-cellular deposition of aggregates composed of misfolded insoluble proteins. These deposits composed of tau, amyloid-β or α-synuclein spread from cell to cell, in a prion-like manner. Emerging evidence suggests that the circulating soluble species of these misfolded proteins (usually referred as oligomers) could play a major role in pathology, while insoluble aggregates would represent their protective less toxic counterparts. Convincing data support the hypothesis that the cellular prion protein, PrP^C, act as a toxicity-transducing receptor for amyloid-β oligomers. As a consequence, several studies extended investigations to the role played by PrP^C in binding aggregates of proteins other than Aβ, such as tau and α-synuclein, for its possible common role in mediating toxic signaling. A better characterization of the biological relevance of PrP^C as key ligand and potential mediator of toxicity for multiple proteinaceous aggregated species, prions or PrP^Sc included, would bring relevant therapeutic implications. Here we will first describe the structure of the prion protein and the hypothesized interplay with its pathological counterpart PrP^Sc and then we will recapitulate the most relevant discoveries regarding the role of PrP^C in the interaction with aggregated forms of other neurodegeneration-associated proteins.

神经退行性疾病总是与由错误折叠的不溶蛋白组成的聚集体在细胞内或细胞外沉积有关。这些由tau，淀粉样蛋白β或α-突触核蛋白组成的沉积物以a病毒样方式从一个细胞扩散到另一个细胞。新兴证据表明，这些错误折叠的蛋白质的循环可溶性物种（通常称为寡聚物）可能在病理学中起主要作用，而不溶性聚集体将代表其毒性较小的保护性对应物。令人信服的数据支持以下假设：细胞病毒蛋白PrP ^C充当淀粉样β-寡聚体的毒性传递受体。结果，一些研究扩大了对PrP ^C的作用的研究。由于其可能在介导毒性信号转导中的常见作用，因此可与Aβ以外的其他蛋白质（例如tau和α-突触核蛋白）的结合聚集体结合。更好地表征PrP ^C作为关键配体和潜在毒性介质对多种蛋白质聚集物种，species病毒或PrP ^Sc的生物学相关性，将带来相关的治疗意义。在这里，我们将首先描述the病毒蛋白的结构及其与病理学对应的PrP ^Sc的假设相互作用，然后我们将概述关于PrP ^C在与其他神经退行相关蛋白的聚集形式相互作用中的作用的最相关发现。