Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.3
3.8
Journals
Viruses
Special Issues
Deciphering the Molecular Targets of Prion and Prion-Like Strains
share announcement

Deciphering the Molecular Targets of Prion and Prion-Like Strains

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Prions".

Deadline for manuscript submissions: closed (31 January 2019) | Viewed by 67632

Special Issue Editor

Dr. Peter Kloehn

E-Mail Website
Guest Editor
MRC Prion Unit at UCL, Institute of Prion Diseases, 33 Cleveland Street, London W1W 7FF, UK
Interests: neuroscience; neurodegeneration; prion diseases; Alzheimer’s disease; proteinopathies

Special Issue Information

Dear Colleagues,

Prion strains are conformational variants of abnormal prion proteins and can be distinguished by differences in disease incubation times, lesion profiles and electrophoretic mobilities. It has long been postulated that differences in clinical phenotypes may be associated with distinct prion strains, but direct evidence for this hypothesis is missing due to the lack of understanding of molecular disease pathways.

While initially attributed to prion diseases, it is now becoming evident that strains of aggregation-prone proteins are found in other neurodegenerative diseases. Recent data on the strain-properties of α-synuclein, Tau, Aβ, SOD1, and TDP-43 suggests that strains may be a ubiquitous phenomenon of pathogenic protein aggregates. Data on selective neuronal vulnerability and distinct clinical phenotypes in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and tauopathies show compelling analogies with those in prion diseases.

This common interest in prion-like mechanisms across disciplines in dementia research creates opportunities to identify the critical targets and disease pathways of neurodegeneration that may be difficult or impossible to infer from the data available to a single discipline. The critical and most challenging question concerns the mechanistic underpinning of the selective neuronal vulnerability of strains. To address this, the most suitable and advanced models, from tissue cultures to mouse models, have to be implemented to provide translatable data.

This Special Issue is a forum to share and publish data and insights on the strain properties of protein aggregates, including recent data on the molecular targets of strains, biological and/or adaptive responses to strains and suggestions for new concepts to decipher the molecular targets of selective neuronal vulnerability.

Dr. Peter Kloehn
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • prion
  • prion-like
  • α-synuclein
  • tau
  • SOD1
  • TDP-43
  • Amyloid beta
  • clincial target area
  • spongiosis
  • selective neuronal vulnerability
  • prion diseases
  • Alzheimer’s disease
  • Parkinson’s disease
  • amyotrophic lateral sclerosis
  • tauopathies
  • frontotemporal dementia

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (12 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

20 pages, 4604 KiB  
Article
A New Cell Model for Investigating Prion Strain Selection and Adaptation
by Alexandra Philiastides, Juan Manuel Ribes, Daniel Chun-Mun Yip, Christian Schmidt, Iryna Benilova and Peter-Christian Klöhn
Viruses 2019, 11(10), 888; https://doi.org/10.3390/v11100888 - 22 Sep 2019
Cited by 4 | Viewed by 4411
Abstract
Prion diseases are fatal neurodegenerative diseases that affect humans and animals. Prion strains, conformational variants of misfolded prion proteins, are associated with distinct clinical and pathological phenotypes. Host-strain interactions result in the selective damage of distinct brain areas and they are responsible for [...] Read more.
Prion diseases are fatal neurodegenerative diseases that affect humans and animals. Prion strains, conformational variants of misfolded prion proteins, are associated with distinct clinical and pathological phenotypes. Host-strain interactions result in the selective damage of distinct brain areas and they are responsible for strain selection and/or adaptation, but the underlying molecular mechanisms are unknown. Prion strains can be distinguished by their cell tropism in vivo and in vitro, which suggests that susceptibility to distinct prion strains is determined by cellular factors. The neuroblastoma cell line PK1 is refractory to the prion strain Me7, but highly susceptible to RML. We challenged a large number of clonal PK1 lines with Me7 and successfully selected highly Me7-susceptible subclones (PME) to investigate whether the prion strain repertoire of PK1 can be expanded. Notably, the Me7-infected PME clones were more protease-resistant when compared to RML-infected PME clones, which suggested that cell-adapted Me7 and RML are distinct prion strains. Strikingly, Me7-refractory cells, including PK1 and astrocytes in cortico-hippocampal cultures, are highly susceptible to prions, being derived from homogenates of Me7-infected PME cells, suggesting that the passage of Me7 in PME cells leads to an extended host range. Thus, PME clones represent a compelling cell model for strain selection and adaptation. Full article
(This article belongs to the Special Issue Deciphering the Molecular Targets of Prion and Prion-Like Strains)
►▼ Show Figures

Figure 1

Review

Jump to: Research

17 pages, 1981 KiB  
Review
Heterogeneity and Architecture of Pathological Prion Protein Assemblies: Time to Revisit the Molecular Basis of the Prion Replication Process?
by Angélique Igel-Egalon, Jan Bohl, Mohammed Moudjou, Laetitia Herzog, Fabienne Reine, Human Rezaei and Vincent Béringue
Viruses 2019, 11(5), 429; https://doi.org/10.3390/v11050429 - 10 May 2019
Cited by 18 | Viewed by 4661
Abstract
Prions are proteinaceous infectious agents responsible for a range of neurodegenerative diseases in animals and humans. Prion particles are assemblies formed from a misfolded, β-sheet rich, aggregation-prone isoform (PrPSc) of the host-encoded cellular prion protein (PrPC). Prions replicate by [...] Read more.
Prions are proteinaceous infectious agents responsible for a range of neurodegenerative diseases in animals and humans. Prion particles are assemblies formed from a misfolded, β-sheet rich, aggregation-prone isoform (PrPSc) of the host-encoded cellular prion protein (PrPC). Prions replicate by recruiting and converting PrPC into PrPSc, by an autocatalytic process. PrPSc is a pleiomorphic protein as different conformations can dictate different disease phenotypes in the same host species. This is the basis of the strain phenomenon in prion diseases. Recent experimental evidence suggests further structural heterogeneity in PrPSc assemblies within specific prion populations and strains. Still, this diversity is rather seen as a size continuum of assemblies with the same core structure, while analysis of the available experimental data points to the existence of structurally distinct arrangements. The atomic structure of PrPSc has not been elucidated so far, making the prion replication process difficult to understand. All currently available models suggest that PrPSc assemblies exhibit a PrPSc subunit as core constituent, which was recently identified. This review summarizes our current knowledge on prion assembly heterogeneity down to the subunit level and will discuss its importance with regard to the current molecular principles of the prion replication process. Full article
(This article belongs to the Special Issue Deciphering the Molecular Targets of Prion and Prion-Like Strains)
►▼ Show Figures

Figure 1

14 pages, 878 KiB  
Review
Impact of Amyloid Polymorphism on Prion-Chaperone Interactions in Yeast
by Andrea N. Killian, Sarah C. Miller and Justin K. Hines
Viruses 2019, 11(4), 349; https://doi.org/10.3390/v11040349 - 16 Apr 2019
Cited by 15 | Viewed by 5170
Abstract
Yeast prions are protein-based genetic elements found in the baker’s yeast Saccharomyces cerevisiae, most of which are amyloid aggregates that propagate by fragmentation and spreading of small, self-templating pieces called propagons. Fragmentation is carried out by molecular chaperones, specifically Hsp104, Hsp70, and [...] Read more.
Yeast prions are protein-based genetic elements found in the baker’s yeast Saccharomyces cerevisiae, most of which are amyloid aggregates that propagate by fragmentation and spreading of small, self-templating pieces called propagons. Fragmentation is carried out by molecular chaperones, specifically Hsp104, Hsp70, and Hsp40. Like other amyloid-forming proteins, amyloid-based yeast prions exhibit structural polymorphisms, termed “strains” in mammalian systems and “variants” in yeast, which demonstrate diverse phenotypes and chaperone requirements for propagation. Here, the known differential interactions between chaperone proteins and yeast prion variants are reviewed, specifically those of the yeast prions [PSI+], [RNQ+]/[PIN+], and [URE3]. For these prions, differences in variant-chaperone interactions (where known) with Hsp104, Hsp70s, Hsp40s, Sse1, and Hsp90 are summarized, as well as some interactions with chaperones of other species expressed in yeast. As amyloid structural differences greatly impact chaperone interactions, understanding and accounting for these variations may be crucial to the study of chaperones and both prion and non-prion amyloids. Full article
(This article belongs to the Special Issue Deciphering the Molecular Targets of Prion and Prion-Like Strains)
►▼ Show Figures

Figure 1

25 pages, 1080 KiB  
Review
All the Same? The Secret Life of Prion Strains within Their Target Cells
by Ina M. Vorberg
Viruses 2019, 11(4), 334; https://doi.org/10.3390/v11040334 - 9 Apr 2019
Cited by 10 | Viewed by 5897
Abstract
Prions are infectious β-sheet-rich protein aggregates composed of misfolded prion protein (PrPSc) that do not possess coding nucleic acid. Prions replicate by recruiting and converting normal cellular PrPC into infectious isoforms. In the same host species, prion strains target distinct [...] Read more.
Prions are infectious β-sheet-rich protein aggregates composed of misfolded prion protein (PrPSc) that do not possess coding nucleic acid. Prions replicate by recruiting and converting normal cellular PrPC into infectious isoforms. In the same host species, prion strains target distinct brain regions and cause different disease phenotypes. Prion strains are associated with biophysically distinct PrPSc conformers, suggesting that strain properties are enciphered within alternative PrPSc quaternary structures. So far it is unknown how prion strains target specific cells and initiate productive infections. Deeper mechanistic insight into the prion life cycle came from cell lines permissive to a range of different prion strains. Still, it is unknown why certain cell lines are refractory to infection by one strain but permissive to another. While pharmacologic and genetic manipulations revealed subcellular compartments involved in prion replication, little is known about strain-specific requirements for endocytic trafficking pathways. This review summarizes our knowledge on how prions replicate within their target cells and on strain-specific differences in prion cell biology. Full article
(This article belongs to the Special Issue Deciphering the Molecular Targets of Prion and Prion-Like Strains)
►▼ Show Figures

Figure 1

27 pages, 1426 KiB  
Review
Understanding Prion Strains: Evidence from Studies of the Disease Forms Affecting Humans
by Marcello Rossi, Simone Baiardi and Piero Parchi
Viruses 2019, 11(4), 309; https://doi.org/10.3390/v11040309 - 29 Mar 2019
Cited by 46 | Viewed by 7750
Abstract
Prion diseases are a unique group of rare neurodegenerative disorders characterized by tissue deposition of heterogeneous aggregates of abnormally folded protease-resistant prion protein (PrPSc), a broad spectrum of disease phenotypes and a variable efficiency of disease propagation in vivo. The dominant [...] Read more.
Prion diseases are a unique group of rare neurodegenerative disorders characterized by tissue deposition of heterogeneous aggregates of abnormally folded protease-resistant prion protein (PrPSc), a broad spectrum of disease phenotypes and a variable efficiency of disease propagation in vivo. The dominant clinicopathological phenotypes of human prion disease include Creutzfeldt–Jakob disease, fatal insomnia, variably protease-sensitive prionopathy, and Gerstmann–Sträussler–Scheinker disease. Prion disease propagation into susceptible hosts led to the isolation and characterization of prion strains, initially operatively defined as “isolates” causing diseases with distinctive characteristics, such as the incubation period, the pattern of PrPSc distribution, and the regional severity of neuropathological changes after injection into syngeneic hosts. More recently, the structural basis of prion strains has been linked to amyloid polymorphs (i.e., variant amyloid protein conformations) and the concept extended to all protein amyloids showing polymorphic structures and some evidence of in vivo or in vitro propagation by seeding. Despite the significant advances, however, the link between amyloid structure and disease is not understood in many instances. Here we reviewed the most significant contributions of human prion disease studies to current knowledge of the molecular basis of phenotypic variability and the prion strain phenomenon and underlined the unsolved issues from the human disease perspective. Full article
(This article belongs to the Special Issue Deciphering the Molecular Targets of Prion and Prion-Like Strains)
►▼ Show Figures

Figure 1

37 pages, 1203 KiB  
Review
Prion and Prion-Like Protein Strains: Deciphering the Molecular Basis of Heterogeneity in Neurodegeneration
by Carlo Scialò, Elena De Cecco, Paolo Manganotti and Giuseppe Legname
Viruses 2019, 11(3), 261; https://doi.org/10.3390/v11030261 - 14 Mar 2019
Cited by 48 | Viewed by 9093
Abstract
Increasing evidence suggests that neurodegenerative disorders share a common pathogenic feature: the presence of deposits of misfolded proteins with altered physicochemical properties in the Central Nervous System. Despite a lack of infectivity, experimental data show that the replication and propagation of neurodegenerative disease-related [...] Read more.
Increasing evidence suggests that neurodegenerative disorders share a common pathogenic feature: the presence of deposits of misfolded proteins with altered physicochemical properties in the Central Nervous System. Despite a lack of infectivity, experimental data show that the replication and propagation of neurodegenerative disease-related proteins including amyloid-β (Aβ), tau, α-synuclein and the transactive response DNA-binding protein of 43 kDa (TDP-43) share a similar pathological mechanism with prions. These observations have led to the terminology of “prion-like” to distinguish between conditions with noninfectious characteristics but similarities with the prion replication and propagation process. Prions are considered to adapt their conformation to changes in the context of the environment of replication. This process is known as either prion selection or adaptation, where a distinct conformer present in the initial prion population with higher propensity to propagate in the new environment is able to prevail over the others during the replication process. In the last years, many studies have shown that prion-like proteins share not only the prion replication paradigm but also the specific ability to aggregate in different conformations, i.e., strains, with relevant clinical, diagnostic and therapeutic implications. This review focuses on the molecular basis of the strain phenomenon in prion and prion-like proteins. Full article
(This article belongs to the Special Issue Deciphering the Molecular Targets of Prion and Prion-Like Strains)
►▼ Show Figures

Figure 1

17 pages, 1228 KiB  
Review
Prion Variants of Yeast are Numerous, Mutable, and Segregate on Growth, Affecting Prion Pathogenesis, Transmission Barriers, and Sensitivity to Anti-Prion Systems
by Reed B. Wickner, Moonil Son and Herman K. Edskes
Viruses 2019, 11(3), 238; https://doi.org/10.3390/v11030238 - 9 Mar 2019
Cited by 17 | Viewed by 4642
Abstract
The known amyloid-based prions of Saccharomyces cerevisiae each have multiple heritable forms, called “prion variants” or “prion strains”. These variants, all based on the same prion protein sequence, differ in their biological properties and their detailed amyloid structures, although each of the few [...] Read more.
The known amyloid-based prions of Saccharomyces cerevisiae each have multiple heritable forms, called “prion variants” or “prion strains”. These variants, all based on the same prion protein sequence, differ in their biological properties and their detailed amyloid structures, although each of the few examined to date have an in-register parallel folded β sheet architecture. Here, we review the range of biological properties of yeast prion variants, factors affecting their generation and propagation, the interaction of prion variants with each other, the mutability of prions, and their segregation during mitotic growth. After early differentiation between strong and weak stable and unstable variants, the parameters distinguishing the variants has dramatically increased, only occasionally correlating with the strong/weak paradigm. A sensitivity to inter- and intraspecies barriers, anti-prion systems, and chaperone deficiencies or excesses and other factors all have dramatic selective effects on prion variants. Recent studies of anti-prion systems, which cure prions in wild strains, have revealed an enormous array of new variants, normally eliminated as they arise and so not previously studied. This work suggests that defects in the anti-prion systems, analogous to immune deficiencies, may be at the root of some human amyloidoses. Full article
(This article belongs to the Special Issue Deciphering the Molecular Targets of Prion and Prion-Like Strains)
►▼ Show Figures

Graphical abstract

13 pages, 1766 KiB  
Review
In vitro Modeling of Prion Strain Tropism
by Etienne Levavasseur, Nicolas Privat and Stéphane Haïk
Viruses 2019, 11(3), 236; https://doi.org/10.3390/v11030236 - 9 Mar 2019
Cited by 1 | Viewed by 3285
Abstract
Prions are atypical infectious agents lacking genetic material. Yet, various strains have been isolated from animals and humans using experimental models. They are distinguished by the resulting pattern of disease, including the localization of PrPsc deposits and the spongiform changes they induce in [...] Read more.
Prions are atypical infectious agents lacking genetic material. Yet, various strains have been isolated from animals and humans using experimental models. They are distinguished by the resulting pattern of disease, including the localization of PrPsc deposits and the spongiform changes they induce in the brain of affected individuals. In this paper, we discuss the emerging use of cellular and acellular models to decipher the mechanisms involved in the strain-specific targeting of distinct brain regions. Recent studies suggest that neuronal cultures, protein misfolding cyclic amplification, and combination of both approaches may be useful to explore this under-investigated but central domain of the prion field. Full article
(This article belongs to the Special Issue Deciphering the Molecular Targets of Prion and Prion-Like Strains)
►▼ Show Figures

Figure 1

9 pages, 1712 KiB  
Review
High-Pressure Response of Amyloid Folds
by Joan Torrent, Davy Martin, Angélique Igel-Egalon, Vincent Béringue and Human Rezaei
Viruses 2019, 11(3), 202; https://doi.org/10.3390/v11030202 - 28 Feb 2019
Cited by 6 | Viewed by 3692
Abstract
The abnormal protein aggregates in progressive neurodegenerative disorders, such as Alzheimer’s, Parkinson’s and prion diseases, adopt a generic structural form called amyloid fibrils. The precise amyloid fold can differ between patients and these differences are related to distinct neuropathological phenotypes of the diseases. [...] Read more.
The abnormal protein aggregates in progressive neurodegenerative disorders, such as Alzheimer’s, Parkinson’s and prion diseases, adopt a generic structural form called amyloid fibrils. The precise amyloid fold can differ between patients and these differences are related to distinct neuropathological phenotypes of the diseases. A key focus in current research is the molecular mechanism governing such structural diversity, known as amyloid polymorphism. In this review, we focus on our recent work on recombinant prion protein (recPrP) and the use of pressure as a variable for perturbing protein structure. We suggest that the amyloid polymorphism is based on volumetric features. Accordingly, pressure is the thermodynamic parameter that fits best to exploit volume differences within the states of a chemical reaction, since it shifts the equilibrium constant to the state that has the smaller volume. In this context, there are analogies with the process of correct protein folding, the high pressure-induced effects of which have been studied for more than a century and which provides a valuable source of inspiration. We present a short overview of this background and review our recent results regarding the folding, misfolding, and aggregation-disaggregation of recPrP under pressure. We present preliminary experiments aimed at identifying how prion protein fibril diversity is related to the quaternary structure by using pressure and varying protein sequences. Finally, we consider outstanding questions and testable mechanistic hypotheses regarding the multiplicity of states in the amyloid fold. Full article
(This article belongs to the Special Issue Deciphering the Molecular Targets of Prion and Prion-Like Strains)
►▼ Show Figures

Figure 1

15 pages, 1765 KiB  
Review
Mechanisms of Strain Diversity of Disease-Associated in-Register Parallel β-Sheet Amyloids and Implications About Prion Strains
by Yuzuru Taguchi, Hiroki Otaki and Noriyuki Nishida
Viruses 2019, 11(2), 110; https://doi.org/10.3390/v11020110 - 28 Jan 2019
Cited by 5 | Viewed by 3621
Abstract
The mechanism of prion strain diversity remains unsolved. Investigation of inheritance and diversification of protein-based pathogenic information demands the identification of the detailed structures of abnormal isoforms of the prion protein (PrPSc); however, achieving purification is difficult without affecting infectivity. Similar [...] Read more.
The mechanism of prion strain diversity remains unsolved. Investigation of inheritance and diversification of protein-based pathogenic information demands the identification of the detailed structures of abnormal isoforms of the prion protein (PrPSc); however, achieving purification is difficult without affecting infectivity. Similar prion-like properties are recognized also in other disease-associated in-register parallel β-sheet amyloids including Tau and α-synuclein (αSyn) amyloids. Investigations into structures of those amyloids via solid-state nuclear magnetic resonance spectroscopy and cryo-electron microscopy recently made remarkable advances due to their relatively small sizes and lack of post-translational modifications. Herein, we review advances regarding pathogenic amyloids, particularly Tau and αSyn, and discuss implications about strain diversity mechanisms of prion/PrPSc from the perspective that PrPSc is an in-register parallel β-sheet amyloid. Additionally, we present our recent data of molecular dynamics simulations of αSyn amyloid, which suggest significance of compatibility between β-sheet propensities of the substrate and local structures of the template for stability of amyloid structures. Detailed structures of αSyn and Tau amyloids are excellent models of pathogenic amyloids, including PrPSc, to elucidate strain diversity and pathogenic mechanisms. Full article
(This article belongs to the Special Issue Deciphering the Molecular Targets of Prion and Prion-Like Strains)
►▼ Show Figures

Figure 1

20 pages, 2679 KiB  
Review
Neuroinflammation, Microglia, and Cell-Association during Prion Disease
by James A. Carroll and Bruce Chesebro
Viruses 2019, 11(1), 65; https://doi.org/10.3390/v11010065 - 15 Jan 2019
Cited by 59 | Viewed by 9179
Abstract
Prion disorders are transmissible diseases caused by a proteinaceous infectious agent that can infect the lymphatic and nervous systems. The clinical features of prion diseases can vary, but common hallmarks in the central nervous system (CNS) are deposition of abnormally folded protease-resistant prion [...] Read more.
Prion disorders are transmissible diseases caused by a proteinaceous infectious agent that can infect the lymphatic and nervous systems. The clinical features of prion diseases can vary, but common hallmarks in the central nervous system (CNS) are deposition of abnormally folded protease-resistant prion protein (PrPres or PrPSc), astrogliosis, microgliosis, and neurodegeneration. Numerous proinflammatory effectors expressed by astrocytes and microglia are increased in the brain during prion infection, with many of them potentially damaging to neurons when chronically upregulated. Microglia are important first responders to foreign agents and damaged cells in the CNS, but these immune-like cells also serve many essential functions in the healthy CNS. Our current understanding is that microglia are beneficial during prion infection and critical to host defense against prion disease. Studies indicate that reduction of the microglial population accelerates disease and increases PrPSc burden in the CNS. Thus, microglia are unlikely to be a foci of prion propagation in the brain. In contrast, neurons and astrocytes are known to be involved in prion replication and spread. Moreover, certain astrocytes, such as A1 reactive astrocytes, have proven neurotoxic in other neurodegenerative diseases, and thus might also influence the progression of prion-associated neurodegeneration. Full article
(This article belongs to the Special Issue Deciphering the Molecular Targets of Prion and Prion-Like Strains)
►▼ Show Figures

Graphical abstract

13 pages, 5689 KiB  
Review
Prion Strain-Specific Structure and Pathology: A View from the Perspective of Glycobiology
by Ilia V. Baskakov, Elizaveta Katorcha and Natallia Makarava
Viruses 2018, 10(12), 723; https://doi.org/10.3390/v10120723 - 18 Dec 2018
Cited by 29 | Viewed by 5173
Abstract
Prion diseases display multiple disease phenotypes characterized by diverse clinical symptoms, different brain regions affected by the disease, distinct cell tropism and diverse PrPSc deposition patterns. The diversity of disease phenotypes within the same host is attributed to the ability of PrP [...] Read more.
Prion diseases display multiple disease phenotypes characterized by diverse clinical symptoms, different brain regions affected by the disease, distinct cell tropism and diverse PrPSc deposition patterns. The diversity of disease phenotypes within the same host is attributed to the ability of PrPC to acquire multiple, alternative, conformationally distinct, self-replicating PrPSc states referred to as prion strains or subtypes. Structural diversity of PrPSc strains has been well documented, yet the question of how different PrPSc structures elicit multiple disease phenotypes remains poorly understood. The current article reviews emerging evidence suggesting that carbohydrates in the form of sialylated N-linked glycans, which are a constitutive part of PrPSc, are important players in defining strain-specific structures and disease phenotypes. This article introduces a new hypothesis, according to which individual strain-specific PrPSc structures govern selection of PrPC sialoglycoforms that form strain-specific patterns of carbohydrate epitopes on PrPSc surface and contribute to defining the disease phenotype and outcomes. Full article
(This article belongs to the Special Issue Deciphering the Molecular Targets of Prion and Prion-Like Strains)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-12
Back to TopTop