Special Issue "Prion Disease"

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

Deadline for manuscript submissions: 15 December 2021.

Special Issue Editor

Dr. Valerie L. Sim
E-Mail Website
Guest Editor
Centre for Prions and Protein Folding Diseases, University of Alberta, 204 Brain and Aging Research Building, Edmonton, AB T6G 2M8, Canada

Special Issue Information

Prion diseases are rare, rapidly progressive neurodegenerative diseases that are associated with the templated misfolding of the normally expressed prion protein. They can be spontaneous, genetic, or acquired, and can be difficult to diagnose in early stages of disease. They are universally fatal and there are no disease-modifying treatments. Studying therapeutics in human prion disease is challenging because of the disease’s rarity, its rapid progression, and the delays in diagnosis.

In the past decade, a number of advancements have been made with respect to diagnosis through brain imaging, such as diffusion-weighted MRI, and methods for detecting disease biomarkers, including the causative misfolded prion protein. These tests have helped make early pre-mortem diagnosis more reliable. In addition, researchers are exploring ways to understand disease biomarkers and progression, particularly in asymptomatic patients with genetic forms of disease. This is opening up new approaches to combating the disease, including targeting the normal form of the prion protein. Advances in the prion field are also aiding the study of other neurodegenerative diseases that share the prion mechanism of propagated protein misfolding.

This Special Issue will focus on current and novel diagnostic approaches to prion and related protein misfolding diseases, advances in the understanding of disease pathogenesis, and how these advances are being applied to the development of therapeutics.

Dr. Valerie L. Sim
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 papers will be 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 2200 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 disease
  • Creutzfeldt–Jakob disease
  • fatal familial insomnia
  • Gerstmann–Sträussler–Scheinker
  • biomarker
  • diagnostics
  • treatments
  • protein folding disease
  • neurodegeneration

Published Papers (4 papers)

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Research

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Article
The Cellular Prion Protein Increases the Uptake and Toxicity of TDP-43 Fibrils
Viruses 2021, 13(8), 1625; https://doi.org/10.3390/v13081625 - 17 Aug 2021
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Abstract
Cytoplasmic aggregation of the primarily nuclear TAR DNA-binding protein 43 (TDP-43) affects neurons in most amyotrophic lateral sclerosis (ALS) and approximately half of frontotemporal lobar degeneration (FTLD) cases. The cellular prion protein, PrPC, has been recognized as a common receptor and [...] Read more.
Cytoplasmic aggregation of the primarily nuclear TAR DNA-binding protein 43 (TDP-43) affects neurons in most amyotrophic lateral sclerosis (ALS) and approximately half of frontotemporal lobar degeneration (FTLD) cases. The cellular prion protein, PrPC, has been recognized as a common receptor and downstream effector of circulating neurotoxic species of several proteins involved in neurodegeneration. Here, capitalizing on our recently adapted TDP-43 real time quaking induced reaction, we set reproducible protocols to obtain standardized preparations of recombinant TDP-43 fibrils. We then exploited two different cellular systems (human SH-SY5Y and mouse N2a neuroblastoma cells) engineered to express low or high PrPC levels to investigate the link between PrPC expression on the cell surface and the internalization of TDP-43 fibrils. Fibril uptake was increased in cells overexpressing either human or mouse prion protein. Increased internalization was associated with detrimental consequences in all PrP-overexpressing cell lines but was milder in cells expressing the human form of the prion protein. As described for other amyloids, treatment with TDP-43 fibrils induced a reduction in the accumulation of the misfolded form of PrPC, PrPSc, in cells chronically infected with prions. Our results expand the list of misfolded proteins whose uptake and detrimental effects are mediated by PrPC, which encompass almost all pathological amyloids involved in neurodegeneration. Full article
(This article belongs to the Special Issue Prion Disease)
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Communication
Preclinical Detection of Alpha-Synuclein Seeding Activity in the Colon of a Transgenic Mouse Model of Synucleinopathy by RT-QuIC
Viruses 2021, 13(5), 759; https://doi.org/10.3390/v13050759 - 26 Apr 2021
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Abstract
In synucleinopathies such as Parkinson’s disease (PD) and dementia with Lewy body (DLB), pathological alpha-synuclein (α-syn) aggregates are found in the gastrointestinal (GI) tract as well as in the brain. In this study, using real-time quaking-induced conversion (RT-QuIC), we investigated the presence of [...] Read more.
In synucleinopathies such as Parkinson’s disease (PD) and dementia with Lewy body (DLB), pathological alpha-synuclein (α-syn) aggregates are found in the gastrointestinal (GI) tract as well as in the brain. In this study, using real-time quaking-induced conversion (RT-QuIC), we investigated the presence of α-syn seeding activity in the brain and colon tissue of G2-3 transgenic mice expressing human A53T α-syn. Here we show that pathological α-syn aggregates with seeding activity were present in the colon of G2-3 mice as early as 3 months old, which is in the presymptomatic stage prior to the observation of any neurological abnormalities. In contrast, α-syn seeding activity was not detectable in 3 month-old mouse brains and only identified at 6 months of age in one of three mice. In the symptomatic stage of 12 months of age, RT-QuIC seeding activity was consistently detectable in both the brain and colon of G2-3 mice. Our results indicate that the RT-QuIC assay can presymptomatically detect pathological α-syn aggregates in the colon of G2-3 mice several months prior to their detection in brain tissue. Full article
(This article belongs to the Special Issue Prion Disease)
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Review

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Review
Clinical Use of Improved Diagnostic Testing for Detection of Prion Disease
Viruses 2021, 13(5), 789; https://doi.org/10.3390/v13050789 - 28 Apr 2021
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Abstract
Prion diseases are difficult to recognize as many symptoms are shared among other neurologic pathologies and the full spectra of symptoms usually do not appear until late in the disease course. Additionally, many commonly used laboratory markers are non-specific to prion disease. The [...] Read more.
Prion diseases are difficult to recognize as many symptoms are shared among other neurologic pathologies and the full spectra of symptoms usually do not appear until late in the disease course. Additionally, many commonly used laboratory markers are non-specific to prion disease. The recent introduction of second-generation real time quaking induced conversion (RT-QuIC) has revolutionized pre-mortem diagnosis of prion disease due to its extremely high sensitivity and specificity. However, RT-QuIC does not provide prognostic data and has decreased diagnostic accuracy in some rarer, atypical prion diseases. The objective of this review is to provide an overview of the current clinical utility of fluid-based biomarkers, neurodiagnostic testing, and brain imaging in the diagnosis of prion disease and to suggest guidelines for their clinical use, with a focus on rarer prion diseases with atypical features. Recent advancements in laboratory-based testing and imaging criteria have shown improved diagnostic accuracy and prognostic potential in prion disease, but because these diagnostic tests are not sensitive in some prion disease subtypes and diagnostic test sensitivities are unknown in the event that CWD transmits to humans, it is important to continue investigations into the clinical utility of various testing modalities. Full article
(This article belongs to the Special Issue Prion Disease)
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Other

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Case Report
Creutzfeldt–Jakob Disease with a Five-Year Clinical Course, Multicentric Cerebellar Prion Plaques and Prior History of Biopsy-Proven Primary Angiitis of the Central Nervous System: A Case for Iatrogenic Exposure?
Viruses 2020, 12(12), 1411; https://doi.org/10.3390/v12121411 - 08 Dec 2020
Viewed by 673
Abstract
Creutzfeldt–Jakob disease (CJD) is a rapidly progressive neurodegenerative disease that can arise spontaneously, genetically, or be acquired through iatrogenic exposure. Most patients die within a year of symptom onset. It is rare, affecting 1–2 per million per year, and the majority of cases [...] Read more.
Creutzfeldt–Jakob disease (CJD) is a rapidly progressive neurodegenerative disease that can arise spontaneously, genetically, or be acquired through iatrogenic exposure. Most patients die within a year of symptom onset. It is rare, affecting 1–2 per million per year, and the majority of cases are sporadic. Primary angiitis of the central nervous system (PACNS) is also rare, affecting 2.4 per million per year. We present a case of an unusually long clinical course of CJD, almost five years, which began with symptoms of apraxia. The patient had biopsy-proven PACNS 16 years prior to clinical presentation, and the site of biopsy was the left parietal lobe. Autopsy revealed multicentric prion plaques in the cerebellum, in the setting of normal genetic testing. The presence of plaques in the cerebellum, and prior neurosurgery, raises the possibility of iatrogenic exposure. We present the details of this case, including pathology from the original biopsy and final autopsy, as well as a review of relevant cases in the literature. Full article
(This article belongs to the Special Issue Prion Disease)
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