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The biological function of the cellular prion protein: an update


Wulf, Marie-Angela; Senatore, Assunta; Aguzzi, Adriano (2017). The biological function of the cellular prion protein: an update. BMC Biology, 15:34.

Abstract

The misfolding of the cellular prion protein (PrPC) causes fatal neurodegenerative diseases. Yet PrPC is highly conserved in mammals, suggesting that it exerts beneficial functions preventing its evolutionary elimination. Ablation of PrPC in mice results in well-defined structural and functional alterations in the peripheral nervous system. Many additional phenotypes were ascribed to the lack of PrPC, but some of these were found to arise from genetic artifacts of the underlying mouse models. Here, we revisit the proposed physiological roles of PrPC in the central and peripheral nervous systems and highlight the need for their critical reassessment using new, rigorously controlled animal models.
The cellular prion protein (PrPC) is a cell surface protein expressed in a variety of different organs and tissues with high expression levels in the central and peripheral nervous systems [1]. It is mainly known for its infamous role in prion diseases, where its misfolding and aggregation cause inevitably fatal neurodegenerative conditions [2]. Prion diseases are transmissible and misfolded prion protein (PrPSc) is—according to the “protein-only hypothesis’”—the only disease-causing agent [3]. Under this view, it is puzzling that a protein underlying such severe diseases is highly conserved throughout mammals [4]. This suggests the existence of distinct benefits and, potentially, important physiological functions.
A definitive, fully satisfactory understanding of the physiological function of PrPC has been lacking for a long time. Very recently, we identified a native function of PrPC in the peripheral nervous system and the underlying mechanism of that function [5]. However, PrPC is also highly expressed in the central nervous system (CNS) and its biological activity there is still far from being clear. This review will focus on the proposed roles of cellular prion protein in the central and peripheral nervous systems.

Abstract

The misfolding of the cellular prion protein (PrPC) causes fatal neurodegenerative diseases. Yet PrPC is highly conserved in mammals, suggesting that it exerts beneficial functions preventing its evolutionary elimination. Ablation of PrPC in mice results in well-defined structural and functional alterations in the peripheral nervous system. Many additional phenotypes were ascribed to the lack of PrPC, but some of these were found to arise from genetic artifacts of the underlying mouse models. Here, we revisit the proposed physiological roles of PrPC in the central and peripheral nervous systems and highlight the need for their critical reassessment using new, rigorously controlled animal models.
The cellular prion protein (PrPC) is a cell surface protein expressed in a variety of different organs and tissues with high expression levels in the central and peripheral nervous systems [1]. It is mainly known for its infamous role in prion diseases, where its misfolding and aggregation cause inevitably fatal neurodegenerative conditions [2]. Prion diseases are transmissible and misfolded prion protein (PrPSc) is—according to the “protein-only hypothesis’”—the only disease-causing agent [3]. Under this view, it is puzzling that a protein underlying such severe diseases is highly conserved throughout mammals [4]. This suggests the existence of distinct benefits and, potentially, important physiological functions.
A definitive, fully satisfactory understanding of the physiological function of PrPC has been lacking for a long time. Very recently, we identified a native function of PrPC in the peripheral nervous system and the underlying mechanism of that function [5]. However, PrPC is also highly expressed in the central nervous system (CNS) and its biological activity there is still far from being clear. This review will focus on the proposed roles of cellular prion protein in the central and peripheral nervous systems.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2 May 2017
Deposited On:17 May 2017 06:55
Last Modified:25 Mar 2018 05:36
Publisher:BioMed Central
ISSN:1741-7007
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1186/s12915-017-0375-5
PubMed ID:28464931
Project Information:
  • : FunderH2020
  • : Grant ID670958
  • : Project TitlePRION2020 - Function and malfunction of the prion protein
  • : FunderFP7
  • : Grant ID278611
  • : Project TitleNEURINOX - NOX enzymes as mediators of inflammation-triggered neurodegeneration: modulating NOX enzymes as novel therapies

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