Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
5.1
3.7
Journals
Pathogens
Special Issues
Prions and Prion-Like Transmissible Protein Pathogens
share announcement

Prions and Prion-Like Transmissible Protein Pathogens

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Prions".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 29973

Special Issue Editors

Prof. Dr. Wenquan Zou

E-Mail Website
Guest Editor
Departments of Pathology and Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
Interests: prion disease; prion infected animals; prion protein
Prof. Dr. Jiyan Ma

E-Mail Website
Co-Guest Editor
Center for Neurodegenerative Science, Van Andel Research Institute,333 Bostwick Avenue N.E, Grand Rapids, MI 49503, USA
Interests: Parkinson’s disease, prion disease, protein aggregation in neurodegenerative diseases, prions, pathogenesis of neurodegenerative

Special Issue Information

Dear Colleagues,

Prions are infectious proteins that are associated with a group of transmissible neurodegenerative diseases in humans and animals, such as Creutzfeldt–Jakob disease in humans, scrapie in sheep and goats, mad cow disease in cattle, and chronic wasting disease in elk and deer. Unlike traditional pathogens such as bacteria and viruses that always require genetic material DNA for their propagation, the infectious prion proteins are able to propagate and duplicate and spread from individual to individual in the absence of DNA. Interestingly, prion-like proteins have also recently been observed in other neurodegenerative diseases, such as Alzheimer disease, Parkinson’s disease, amyotrophic lateral sclerosis, etc. These share the prion-like features of propagation and transmission from cell to cell, although in contrast to prions, transmission from individual to individual has not be reported in these prion-like misfolded proteins. Now, prions have become the prototypes for these emerging groups of transmissible protein pathogens.
The annual international Prion conference will take place from May 21–24, 2019 in Edmonton, Alberta, Canada. This Special Issue welcomes prion researchers and experts who wish to highlight new developments in prions and prion-like transmissible misfolded protein pathogens that emerge in the conference. In addition, we shall also accept original research and review articles about pathogenesis, diagnosis, and potential therapeutic responses to human and animal prion diseases. We especially seek manuscripts that report emerging atypical prions and prion diseases as well as innovative strategies and methods for the determination of prions and treatment of prion diseases.
We look forward to your contributions and to a valuable Special Edition that will promote further developments in this exciting field.

Prof. Wenquan Zou
Prof. Jiyan Ma
Guest Editors

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. Pathogens 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 2700 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

  • Prions
  • Prion diseases
  • Prion-like
  • Prion 2019 conference
  • Neurodegenerative disorders
  • Protein misfolding disorders
  • Protein aggregations
  • Neuroscience
  • Alzheimer’s disease
  • Parkinson’s disease
  • Glycosylation

Published Papers (9 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, 1414 KiB  
Article
Discrimination of Classical and Atypical BSE by a Distinct Immunohistochemical PrPSc Profile
by Christine Fast, Catherine Graham, Martin Kaatz, Kristina Santiago-Mateo, Tammy Kaatz, Kendra MacPherson, Anne Balkema-Buschmann, Ute Ziegler, Martin H. Groschup and Stefanie Czub
Pathogens 2023, 12(2), 353; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens12020353 - 20 Feb 2023
Cited by 1 | Viewed by 1373
Abstract
Bovine spongiform encephalopathy (BSE) belongs to the group of transmissible spongiform encephalopathies and is associated with the accumulation of a pathological isoform of the host-encoded glycoprotein, designated prion protein (PrPSc). Classical BSE (C-type) and two atypical BSE forms (L- and H-type) [...] Read more.
Bovine spongiform encephalopathy (BSE) belongs to the group of transmissible spongiform encephalopathies and is associated with the accumulation of a pathological isoform of the host-encoded glycoprotein, designated prion protein (PrPSc). Classical BSE (C-type) and two atypical BSE forms (L- and H-type) are known, and can be discriminated by biochemical characteristics. The goal of our study was to identify type-specific PrPSc profiles by using Immunohistochemistry. In our study, brain samples from 21 cattle, intracerebrally inoculated with C-, H-, and L-type BSE, were used. In addition, the corresponding samples from three orally C-type BSE infected animals were also included. From all animals, a lesion and PrPSc-profiles of six brain regions were determined. The lesion profile and the neuroanatomical distribution of PrPSc was highly consistent between the groups, but the immunohistochemical analysis revealed a distinct PrPSc profile for the different BSE-types, which included both the topographic and cellular pattern of PrPSc. This qualitative and quantitative analysis of PrPSc affected structures sheds new light into the pathogenesis of the different BSE types. Furthermore, immunohistochemical characterization is supported as an additional diagnostic tool in BSE surveillance programs, especially when only formalin-fixed tissue samples are available. Full article
(This article belongs to the Special Issue Prions and Prion-Like Transmissible Protein Pathogens)
►▼ Show Figures

Figure 1

13 pages, 3753 KiB  
Article
Hexameric Aggregation Nucleation Core Sequences and Diversity of Pathogenic Tau Strains
by Ling Wu, Sidharth S. Madhavan, Christopher Tan and Bin Xu
Pathogens 2022, 11(12), 1559; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11121559 - 19 Dec 2022
Cited by 3 | Viewed by 1575
Abstract
Tau aggregation associates with multiple neurodegenerative diseases including Alzheimer’s disease and rare tauopathies such as Pick’s disease, progressive supranuclear palsy, and corticobasal degeneration. The molecular and structural basis of tau aggregation and related diverse misfolded tau strains are not fully understood. To further [...] Read more.
Tau aggregation associates with multiple neurodegenerative diseases including Alzheimer’s disease and rare tauopathies such as Pick’s disease, progressive supranuclear palsy, and corticobasal degeneration. The molecular and structural basis of tau aggregation and related diverse misfolded tau strains are not fully understood. To further understand tau-protein aggregation mechanisms, we performed systematic truncation mutagenesis and mapped key segments of tau proteins that contribute to tau aggregation, where it was determined that microtubule binding domains R2 and R3 play critical roles. We validated that R2- or R3-related hexameric PHF6 and PHF6* peptide sequences are necessary sequences that render tau amyloidogenicity. We also determined that the consensus VQI peptide sequence is not sufficient for amyloidogenicity. We further proposed single- and dual-nucleation core-based strain classifications based on recent cryo-EM structures. We analyzed the structural environment of the hexameric peptide sequences in diverse tau strains in tauopathies that, in part, explains why the VQI consensus core sequence is not sufficient to induce tau aggregation. Our experimental work and complementary structural analysis highlighted the indispensible roles of the hexameric core sequences, and shed light on how the interaction environment of these core sequences contributes to diverse pathogenic tau-strains formation in various tauopathy brains. Full article
(This article belongs to the Special Issue Prions and Prion-Like Transmissible Protein Pathogens)
►▼ Show Figures

Figure 1

21 pages, 3875 KiB  
Article
Further Characterization of Glycoform-Selective Prions of Variably Protease-Sensitive Prionopathy
by Weiguanliu Zhang, Xiangzhu Xiao, Mingxuan Ding, Jue Yuan, Aaron Foutz, Mohammed Moudjou, Tetsuyuki Kitamoto, Jan P. M. Langeveld, Li Cui and Wen-Quan Zou
Pathogens 2021, 10(5), 513; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10050513 - 23 Apr 2021
Cited by 7 | Viewed by 2725
Abstract
Prion is an infectious protein (PrPSc) that is derived from a cellular glycoprotein (PrPC) through a conformational transition and associated with a group of prion diseases in animals and humans. Characterization of proteinase K (PK)-resistant PrPSc by western [...] Read more.
Prion is an infectious protein (PrPSc) that is derived from a cellular glycoprotein (PrPC) through a conformational transition and associated with a group of prion diseases in animals and humans. Characterization of proteinase K (PK)-resistant PrPSc by western blotting has been critical to diagnosis and understanding of prion diseases including Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker (GSS) disease in humans. However, formation as well as biochemical and biological properties of the glycoform-selective PrPSc in variably protease-sensitive prionopathy (VPSPr) remain poorly understood. Here we reveal that formation of the ladder-like PrPSc in VPSPr is a PK-dependent two-step process, which is enhanced by basic pH. Two sets of PrPSc fragments can be identified with antibodies directed against an intermediate or a C-terminal domain of the protein. Moreover, antibodies directed against specific PrP glycoforms reveal faster electrophoretic migrations of PrP fragments mono-glycosylated at residue 181 and 197 in VPSPr than those in sporadic CJD (sCJD). Finally, RT-QuIC assay indicates that PrPSc-seeding activity is lower and its lag time is longer in VPSPr than in sCJD. Our results suggest that the glycoform-selective PrPSc in VPSPr is associated with altered glycosylation, resulting in different PK-truncation and aggregation seeding activity compared to PrPSc in sCJD. Full article
(This article belongs to the Special Issue Prions and Prion-Like Transmissible Protein Pathogens)
►▼ Show Figures

Figure 1

9 pages, 1050 KiB  
Article
Clinical and Laboratory Features of Three Rare Chinese V210I gCJD Patients
by Kang Xiao, Wei Zhou, Li-Ping Gao, Yue-Zhang Wu, Yuan Wang, Cao Chen, Chen Gao, Qi Shi and Xiao-Ping Dong
Pathogens 2020, 9(10), 800; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9100800 - 28 Sep 2020
Cited by 2 | Viewed by 1962
Abstract
Genetic human prion diseases are a group of inherited encephalopathies directly associated with different mutations in PrP-encoding gene PRNP, including more than 50 different mutations worldwide. Some genotypes of mutations show ethno-correlation, and among them, genetic Creutzfeldt–Jacob disease (gCJD) with V210I mutation [...] Read more.
Genetic human prion diseases are a group of inherited encephalopathies directly associated with different mutations in PrP-encoding gene PRNP, including more than 50 different mutations worldwide. Some genotypes of mutations show ethno-correlation, and among them, genetic Creutzfeldt–Jacob disease (gCJD) with V210I mutation is frequent in European countries but rare in East Asia. Here, we comparatively analyzed the clinical and laboratory features of three Chinese patients with V210I mutant identified via the Chinese National CJD Surveillance System (CNS-CJD) in 2019. Two cases were Han Chinese and one was Hui Chinese, without blood kinship. The onset ages of three cases were 69, 64, and 59 years old, respectively. The clinical features of V210I gCJD were similar to sporadic CJD (sCJD), displaying typical clinical symptoms and signs, except that Case 3 did not show myoclonic movement. All three cases displayed sCJD-associated abnormalities on MRI and positive CSF 14-3-3, while two cases recorded typical EEG abnormalities. Only one case was positive in CSF real-time quaking-induced conversion (RT-QuIC). Appearances of mutism in three cases were relatively fast, with the intervals of 30 to 50 days after onset. Family history was not reported in all three cases. Those V210I gCJD cases are rare in China, and probably the first three in East Asia. Full article
(This article belongs to the Special Issue Prions and Prion-Like Transmissible Protein Pathogens)
►▼ Show Figures

Figure 1

12 pages, 1649 KiB  
Article
Pathogenic Prion Protein Isoforms Are Not Present in Cerebral Organoids Generated from Asymptomatic Donors Carrying the E200K Mutation Associated with Familial Prion Disease
by Simote T. Foliaki, Bradley R. Groveman, Jue Yuan, Ryan Walters, Shulin Zhang, Paul Tesar, Wenquan Zou and Cathryn L. Haigh
Pathogens 2020, 9(6), 482; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9060482 - 18 Jun 2020
Cited by 18 | Viewed by 3060
Abstract
Cerebral organoids (COs) are a self-organizing three-dimensional brain tissue mimicking the human cerebral cortex. COs are a promising new system for modelling pathological features of neurological disorders, including prion diseases. COs expressing normal prion protein (PrPC) are susceptible to prion infection when exposed [...] Read more.
Cerebral organoids (COs) are a self-organizing three-dimensional brain tissue mimicking the human cerebral cortex. COs are a promising new system for modelling pathological features of neurological disorders, including prion diseases. COs expressing normal prion protein (PrPC) are susceptible to prion infection when exposed to the disease isoforms of PrP (PrPD). This causes the COs to develop aspects of prion disease pathology considered hallmarks of disease, including the production of detergent-insoluble, protease-resistant misfolded PrPD species capable of seeding the production of more misfolded species. To determine whether COs can model aspects of familial prion diseases, we produced COs from donor fibroblasts carrying the E200K mutation, the most common cause of human familial prion disease. The mature E200K COs were assessed for the hallmarks of prion disease. We found that up to 12 months post-differentiation, E200K COs harbored no PrPD as confirmed by the absence of detergent-insoluble, protease-resistant, and seeding-active PrP species. Our results suggest that the presence of the E200K mutation within the prion gene is insufficient to cause disease in neuronal tissue. Therefore, other factors, such as further genetic modifiers or aging processes, may influence the onset of misfolding. Full article
(This article belongs to the Special Issue Prions and Prion-Like Transmissible Protein Pathogens)
►▼ Show Figures

Figure 1

9 pages, 1207 KiB  
Article
Long-Term Incubation PrPCWD with Soils Affects Prion Recovery but Not Infectivity
by Alsu Kuznetsova, Debbie McKenzie, Catherine Cullingham and Judd M. Aiken
Pathogens 2020, 9(4), 311; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9040311 - 23 Apr 2020
Cited by 15 | Viewed by 3776
Abstract
Chronic wasting disease (CWD) is a contagious prion disease of cervids. The infectious agent is shed from animals at the preclinical and clinical stages of disease where it persists in the environment as a reservoir of CWD infectivity. In this study, we demonstrate [...] Read more.
Chronic wasting disease (CWD) is a contagious prion disease of cervids. The infectious agent is shed from animals at the preclinical and clinical stages of disease where it persists in the environment as a reservoir of CWD infectivity. In this study, we demonstrate that long-term incubation of CWD prions (generated from tg-mice infected with deer or elk prions) with illite, montmorillonite (Mte) and whole soils results in decreased recovery of PrPCWD, suggesting that binding becomes more avid and irreversible with time. This continual decline of immunoblot PrPCWD detection did not correlate with prion infectivity levels. Bioassay showed no significant differences in incubation periods between mice inoculated with 1% CWD brain homogenate (BH) and with the CWD-BH pre-incubated with quartz or Luvisolic Ae horizon for 1 or 30 weeks. After 55 weeks incubation with Chernozem and Luvisol, bound PrPCWD was not detectable by immunoblotting but remained infectious. This study shows that although recovery of PrPCWD bound to soil minerals and whole soils with time become more difficult, prion infectivity is not significantly altered. Detection of prions in soil is, therefore, not only affected by soil type but also by length of time of the prion–soil interaction. Full article
(This article belongs to the Special Issue Prions and Prion-Like Transmissible Protein Pathogens)
►▼ Show Figures

Figure 1

11 pages, 1257 KiB  
Article
PrPSc with Seeding Activity Extensively Overlaps with Proteinase-Resistant PrPSc Rather than Infectious PrPSc
by Yoshifumi Iwamaru, Yuichi Matsuura and Kohtaro Miyazawa
Pathogens 2020, 9(3), 241; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9030241 - 24 Mar 2020
Cited by 3 | Viewed by 3764
Abstract
The disease-associated prion protein (PrPSc) has the ability to seed the conformational conversion of normal prion proteins into the amyloid fibril form. This prion seeding activity can be measured using an in vitro amplification assay termed real-time quaking-induced conversion (RT-QuIC). There is a [...] Read more.
The disease-associated prion protein (PrPSc) has the ability to seed the conformational conversion of normal prion proteins into the amyloid fibril form. This prion seeding activity can be measured using an in vitro amplification assay termed real-time quaking-induced conversion (RT-QuIC). There is a strong correlation between RT-QuIC positivity and prion infection; however, the relationship between seeding activity and infectivity remains elusive. In this study, we used endpoint dilution RT-QuIC on the brain homogenates from wild-type mice with mouse-adopted bovine spongiform encephalopathy (mBSE) at defined intervals during the incubation period and evaluated the temporal relationship among prion seeding dose, levels of proteinase-resistant PrPSc (PrPres), and infectious titer. We found that the infectious titer reached a plateau by 100 days postinfection, whereas seeding dose and PrPres levels were continuously elevated. Our calculation showed that the doubling time (dt) for seeding dose from 40 to 100 days postinoculation was closer to the dt for PrPres levels than to the dt for prion titer. Although an uncoupling of seeding doses and PrPres levels was observed at end-stage disease in this model, our findings suggest that there is substantial but not complete overlap between PrPSc with seeding activity and PrPres rather than infectious PrPSc. Full article
(This article belongs to the Special Issue Prions and Prion-Like Transmissible Protein Pathogens)
►▼ Show Figures

Figure 1

Review

Jump to: Research

15 pages, 1192 KiB  
Review
Modulation of Neuroinflammation by the Gut Microbiota in Prion and Prion-Like Diseases
by Josephine Trichka and Wen-Quan Zou
Pathogens 2021, 10(7), 887; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10070887 - 13 Jul 2021
Cited by 7 | Viewed by 4395
Abstract
The process of neuroinflammation contributes to the pathogenic mechanism of many neurodegenerative diseases. The deleterious attributes of neuroinflammation involve aberrant and uncontrolled activation of glia, which can result in damage to proximal brain parenchyma. Failure to distinguish self from non-self, as well as [...] Read more.
The process of neuroinflammation contributes to the pathogenic mechanism of many neurodegenerative diseases. The deleterious attributes of neuroinflammation involve aberrant and uncontrolled activation of glia, which can result in damage to proximal brain parenchyma. Failure to distinguish self from non-self, as well as leukocyte reaction to aggregation and accumulation of proteins in the CNS, are the primary mechanisms by which neuroinflammation is initiated. While processes local to the CNS may instigate neurodegenerative disease, the existence or dysregulation of systemic homeostasis can also serve to improve or worsen CNS pathologies, respectively. One fundamental component of systemic homeostasis is the gut microbiota, which communicates with the CNS via microbial metabolite production, the peripheral nervous system, and regulation of tryptophan metabolism. Over the past 10–15 years, research focused on the microbiota–gut–brain axis has culminated in the discovery that dysbiosis, or an imbalance between commensal and pathogenic gut bacteria, can promote CNS pathologies. Conversely, a properly regulated and well-balanced microbiome supports CNS homeostasis and reduces the incidence and extent of pathogenic neuroinflammation. This review will discuss the role of the gut microbiota in exacerbating or alleviating neuroinflammation in neurodegenerative diseases, and potential microbiota-based therapeutic approaches to reduce pathology in diseased states. Full article
(This article belongs to the Special Issue Prions and Prion-Like Transmissible Protein Pathogens)
►▼ Show Figures

Figure 1

18 pages, 323 KiB  
Review
Immunotherapy against Prion Disease
by Yue Ma and Jiyan Ma
Pathogens 2020, 9(3), 216; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9030216 - 14 Mar 2020
Cited by 16 | Viewed by 5140
Abstract
The term “prion disease” encompasses a group of neurodegenerative diseases affecting both humans and animals. Currently, there is no effective therapy and all forms of prion disease are invariably fatal. Because of (a) the outbreak of bovine spongiform encephalopathy in cattle and variant [...] Read more.
The term “prion disease” encompasses a group of neurodegenerative diseases affecting both humans and animals. Currently, there is no effective therapy and all forms of prion disease are invariably fatal. Because of (a) the outbreak of bovine spongiform encephalopathy in cattle and variant Creutzfeldt–Jakob disease in humans; (b) the heated debate about the prion hypothesis; and (c) the availability of a natural prion disease in rodents, the understanding of the pathogenic process in prion disease is much more advanced compared to that of other neurodegenerative disorders, which inspired many attempts to develop therapeutic strategies against these fatal diseases. In this review, we focus on immunotherapy against prion disease. We explain our rationale for immunotherapy as a plausible therapeutic choice, review previous trials using either active or passive immunization, and discuss potential strategies for overcoming the hurdles in developing a successful immunotherapy. We propose that immunotherapy is a plausible and practical therapeutic strategy and advocate more studies in this area to develop effective measures to control and treat these devastating disorders. Full article
(This article belongs to the Special Issue Prions and Prion-Like Transmissible Protein Pathogens)
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-9
Back to TopTop