Glial Cell Biology Laboratory, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Cell Morphogenesis Laboratory, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
J Mol Med (Berl). 2022 Oct;100(10):1405-1425. doi: 10.1007/s00109-022-02245-9. Epub 2022 Sep 3.
Cellular prion protein (PrP) is a highly conserved glycoprotein, present both anchored in the cell membrane and soluble in the extracellular medium. It has a diversity of ligands and is variably expressed in numerous tissues and cell subtypes, most notably in the central nervous system (CNS). Its importance has been brought to light over the years both under physiological conditions, such as embryogenesis and immune system homeostasis, and in pathologies, such as cancer and neurodegenerative diseases. During development, PrP plays an important role in CNS, participating in axonal growth and guidance and differentiation of glial cells, but also in other organs such as the heart, lung, and digestive system. In diseases, PrP has been related to several types of tumors, modulating cancer stem cells, enhancing malignant properties, and inducing drug resistance. Also, in non-neoplastic diseases, such as Alzheimer's and Parkinson's diseases, PrP seems to alter the dynamics of neurotoxic aggregate formation and, consequently, the progression of the disease. In this review, we explore in detail the multiple functions of this protein, which proved to be relevant for understanding the dynamics of organism homeostasis, as well as a promising target in the treatment of both neoplastic and degenerative diseases.
细胞朊蛋白（PrP）是一种高度保守的糖蛋白，既锚定在细胞膜上，又可溶解在细胞外基质中。它有多种配体，在许多组织和细胞亚型中表达不同，在中枢神经系统（CNS）中尤为明显。近年来，无论是在胚胎发生和免疫系统稳态等生理条件下，还是在癌症和神经退行性疾病等病理条件下，它的重要性都得到了充分的揭示。在发育过程中，PrP 在中枢神经系统中发挥重要作用，参与轴突生长和神经胶质细胞的分化，但也在心脏、肺和消化系统等其他器官中发挥作用。在疾病中，PrP 与多种类型的肿瘤有关，调节肿瘤干细胞，增强恶性特性，并诱导耐药性。此外，在非肿瘤性疾病中，如阿尔茨海默病和帕金森病，PrP 似乎改变了神经毒性聚集物形成的动力学，从而影响疾病的进展。在这篇综述中，我们详细探讨了这种蛋白质的多种功能，它对于理解机体稳态的动力学具有重要意义，并且是治疗肿瘤和退行性疾病的有前途的靶点。
