Functions of the cellular prion protein, the end of Moore's law, and Ockham's razor theory

Rı́o, José Antonio del; Gavı́n, Rosalina

doi:10.1080/19336896.2015.1126038

Cited by 16 publications

(18 citation statements)

References 112 publications

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“…There is increasing recognition of the contribution of Prnp flanking genes to phenotypes displayed by PrP C -knockout mice that were generated on mixed genetic backgrounds, an issue that confounds interpretation of many studies connecting PrP C to the regulation of neuronal excitability—this problem is documented in more detail in a couple of recent review articles (Striebel et al, 2013a; del Rio and Gavin, 2016). Nevertheless, there are data from animal models other than mice that support the involvement of PrP C in the modulation of neuronal excitability.…”

Section: Prpc Functionmentioning

confidence: 99%

Physiological Functions of the Cellular Prion Protein

Castle

Gill

2017

Front. Mol. Biosci.

168

157

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The prion protein, PrPC, is a small, cell-surface glycoprotein notable primarily for its critical role in pathogenesis of the neurodegenerative disorders known as prion diseases. A hallmark of prion diseases is the conversion of PrPC into an abnormally folded isoform, which provides a template for further pathogenic conversion of PrPC, allowing disease to spread from cell to cell and, in some circumstances, to transfer to a new host. In addition to the putative neurotoxicity caused by the misfolded form(s), loss of normal PrPC function could be an integral part of the neurodegenerative processes and, consequently, significant research efforts have been directed toward determining the physiological functions of PrPC. In this review, we first summarise important aspects of the biochemistry of PrPC before moving on to address the current understanding of the various proposed functions of the protein, including details of the underlying molecular mechanisms potentially involved in these functions. Over years of study, PrPC has been associated with a wide array of different cellular processes and many interacting partners have been suggested. However, recent studies have cast doubt on the previously well-established links between PrPC and processes such as stress-protection, copper homeostasis and neuronal excitability. Instead, the functions best-supported by the current literature include regulation of myelin maintenance and of processes linked to cellular differentiation, including proliferation, adhesion, and control of cell morphology. Intriguing connections have also been made between PrPC and the modulation of circadian rhythm, glucose homeostasis, immune function and cellular iron uptake, all of which warrant further investigation.

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Section: Prpc Functionmentioning

confidence: 99%

Physiological Functions of the Cellular Prion Protein

Castle

Gill

2017

Front. Mol. Biosci.

168

157

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“…Since the generation of the first knock-out (Prnp 0/0 ) mice of PrP C in 1992, referred to as Zürich 1 [57], researchers have used different Prnp 0/0 mice in their studies (Zürich 1 [58], Edinburgh [59], and Zürich 3 [60]) to validate/reveal processes sustained by the functions of the protein (see also [61,62]). Moreover, the number of functions is paralleled by the numerous descriptions of PrP C interactions [63][64][65][66].…”

Section: Prp C and Neuroprotectionmentioning

confidence: 99%

The Quest for Cellular Prion Protein Functions in the Aged and Neurodegenerating Brain

Gavı́n

Lidón

Ferrer

et al. 2020

Cells

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Cellular (also termed ‘natural’) prion protein has been extensively studied for many years for its pathogenic role in prionopathies after misfolding. However, neuroprotective properties of the protein have been demonstrated under various scenarios. In this line, the involvement of the cellular prion protein in neurodegenerative diseases other than prionopathies continues to be widely debated by the scientific community. In fact, studies on knock-out mice show a vast range of physiological functions for the protein that can be supported by its ability as a cell surface scaffold protein. In this review, we first summarize the most commonly described roles of cellular prion protein in neuroprotection, including antioxidant and antiapoptotic activities and modulation of glutamate receptors. Second, in light of recently described interaction between cellular prion protein and some amyloid misfolded proteins, we will also discuss the molecular mechanisms potentially involved in protection against neurodegeneration in pathologies such as Alzheimer’s, Parkinson’s, and Huntington’s diseases.

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“…Two domains can be clearly identified: the N-terminal, unstructured and positively charged, and the C-terminal, globular and structured (3 a-helices, 2 ß sheets and a short tail) [17]. PrP C plays an important role in several cellular functions, spanning from cell cycle and proliferation to copper homeostasis and neuroprotection [18,19]. Recently, other functions were attributed to PrP C , that is acting as a receptor for amyloid-ß (Aß) oligomers [20] and mediating the Aß-induced synaptic dysfunction.…”

Section: The Cellular Prion Protein Acts As a Receptor Of Aggregated mentioning

confidence: 99%

The role of the prion protein in the internalization of α-synuclein amyloids

Cecco

Legname

2018

Prion

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Synucleinopathies are a group of neurodegenerative diseases characterized by the accumulation of α-synuclein amyloids in several regions of the brain. α-Synuclein fibrils are able to spread via cell-to-cell transfer, and once inside the cells, they can template the misfolding and aggregation of the endogenous α-synuclein. Multiple mechanisms have been shown to participate in the process of propagation: endocytosis, tunneling nanotubes and macropinocytosis. Recently, we published a research showing that the cellular form of the prion protein (PrP) acts as a receptor for α-synuclein amyloid fibrils, facilitating their internalization through and endocytic pathway. This interaction occurs by a direct interaction between the fibrils and the N-terminal domain of PrP. In cell lines expressing the pathological form of PrP (PrP), the binding between PrP and α-synuclein fibrils prevents the formation and accumulation of PrP, since PrP is no longer available as a substrate for the pathological conversion templated by PrP. On the contrary, PrP deposits are cleared over passages, probably due to the increased processing of PrP into the neuroprotective fragments N1 and C1. Starting from these data, in this work we present new insights into the role of PrP in the internalization of protein amyloids and the possible therapeutic applications of these findings.

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Functions of the cellular prion protein, the end of Moore's law, and Ockham's razor theory

Cited by 16 publications

References 112 publications

Physiological Functions of the Cellular Prion Protein

Physiological Functions of the Cellular Prion Protein

The Quest for Cellular Prion Protein Functions in the Aged and Neurodegenerating Brain

The role of the prion protein in the internalization of α-synuclein amyloids

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