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The multiple functions of PrPC in physiological, cancer, and neurodegenerative contexts

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Abstract

Cellular prion protein (PrPC) 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, PrPC 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, PrPC 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, PrPC 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.

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Acknowledgements

We thank Sidney Pratt, Canadian, MAT (The Johns Hopkins University), RSAdip—TESL (Cambridge University) for carefully reviewing the English text of this paper.

Funding

This work was supported by Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ; grant number: E-26/200–813/2021); Instituto Nacional de Neurociência Translacional (INNT; grant number: 465346/2014–6); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; grant number: 310350/2020–4), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; grant number: 88881.370888/2019–01), and PhD-Program on Morphological Sciences from Universidade Federal do Rio de Janeiro (UFRJ).

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  1. Glial Cell Biology Laboratory, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil

    Izabella Grimaldi, Felipe Saceanu Leser, José Marcos Janeiro, Bárbara Gomes da Rosa, Ana Clara Campanelli & Flavia Regina Souza Lima

  2. Cell Morphogenesis Laboratory, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil

    Luciana Romão

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Conceptualization: Izabella Grimaldi and Flavia Lima. Literature search: Izabella Grimaldi, Ana Clara Campanelli, Felipe Saceanu Leser, José Marcos Janeiro, and Bárbara Gomes da Rosa. Writing—original draft preparation: Izabella Grimaldi, Ana Clara Campanelli, José Marcos Janeiro, Felipe Saceanu Leser, and Bárbara Gomes da Rosa. Writing—review and editing: Izabella Grimaldi, Felipe Saceanu Leser, Luciana Romão,and Flavia Lima. Supervision: Flavia Lima and Luciana Romão. All authors read and approved the final version of the manuscript.

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Correspondence to Flavia Regina Souza Lima.

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Grimaldi, I., Leser, F.S., Janeiro, J.M. et al. The multiple functions of PrPC in physiological, cancer, and neurodegenerative contexts. J Mol Med 100, 1405–1425 (2022). https://doi.org/10.1007/s00109-022-02245-9

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