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Viruses Dec 2021Prion diseases, also known as transmissible spongiform encephalopathies (TSEs), are a group of neurodegenerative protein misfolding diseases that invariably cause death.... (Review)
Review
Prion diseases, also known as transmissible spongiform encephalopathies (TSEs), are a group of neurodegenerative protein misfolding diseases that invariably cause death. TSEs occur when the endogenous cellular prion protein (PrP) misfolds to form the pathological prion protein (PrP), which templates further conversion of PrP to PrP, accumulates, and initiates a cascade of pathologic processes in cells and tissues. Different strains of prion disease within a species are thought to arise from the differential misfolding of the prion protein and have different clinical phenotypes. Different strains of prion disease may also result in differential accumulation of PrP in brain regions and tissues of natural hosts. Here, we review differential accumulation that occurs in the retinal ganglion cells, cerebellar cortex and white matter, and plexuses of the enteric nervous system in cattle with bovine spongiform encephalopathy, sheep and goats with scrapie, cervids with chronic wasting disease, and humans with prion diseases. By characterizing TSEs in their natural host, we can better understand the pathogenesis of different prion strains. This information is valuable in the pursuit of evaluating and discovering potential biomarkers and therapeutics for prion diseases.
Topics: Animals; Humans; Prion Diseases; Prion Proteins; Protein Folding; Proteostasis Deficiencies
PubMed: 34960722
DOI: 10.3390/v13122453 -
Progress in Neurobiology Nov 2013This paper is intended to discuss some of the scientific and ethical issues that are created by increased research efforts towards earlier diagnosis, as well as to...
This paper is intended to discuss some of the scientific and ethical issues that are created by increased research efforts towards earlier diagnosis, as well as to treatment of, human prion diseases (and related dementias), including the resulting consequences for individuals, their families, and society. Most patients with prion disease currently are diagnosed when they are about 2/3 of the way through their disease course (Geschwind et al., 2010a; Paterson et al., 2012b), when the disease has progressed so far that even treatments that stop the disease process would probably have little benefit. Although there are currently no treatments available for prion diseases, we and others have realized that we must diagnose patients earlier and with greater accuracy so that future treatments have hope of success. As approximately 15% of prion diseases have a autosomal dominant genetic etiology, this further adds to the complexity of ethical issues, particularly regarding when to conduct genetic testing, release of genetic results, and when or if to implement experimental therapies. Human prion diseases are both infectious and transmissible; great care is required to balance the needs of the family and individual with both public health needs and strained hospital budgets. It is essential to proactively examine and address the ethical issues involved, as well as to define and in turn provide best standards of care.
Topics: Animals; Biomedical Research; Humans; Neurology; Prion Diseases
PubMed: 23906487
DOI: 10.1016/j.pneurobio.2013.07.001 -
Neurosurgical Focus Jul 2016The human prion diseases, or transmissible spongiform encephalopathies, have captivated our imaginations since their discovery in the Fore linguistic group in Papua New... (Review)
Review
The human prion diseases, or transmissible spongiform encephalopathies, have captivated our imaginations since their discovery in the Fore linguistic group in Papua New Guinea in the 1950s. The mysterious and poorly understood "infectious protein" has become somewhat of a household name in many regions across the globe. From bovine spongiform encephalopathy (BSE), commonly identified as mad cow disease, to endocannibalism, media outlets have capitalized on these devastatingly fatal neurological conditions. Interestingly, since their discovery, there have been more than 492 incidents of iatrogenic transmission of prion diseases, largely resulting from prion-contaminated growth hormone and dura mater grafts. Although fewer than 9 cases of probable iatrogenic neurosurgical cases of Creutzfeldt-Jakob disease (CJD) have been reported worldwide, the likelihood of some missed cases and the potential for prion transmission by neurosurgery create considerable concern. Laboratory studies indicate that standard decontamination and sterilization procedures may be insufficient to completely remove infectivity from prion-contaminated instruments. In this unfortunate event, the instruments may transmit the prion disease to others. Much caution therefore should be taken in the absence of strong evidence against the presence of a prion disease in a neurosurgical patient. While the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have devised risk assessment and decontamination protocols for the prevention of iatrogenic transmission of the prion diseases, incidents of possible exposure to prions have unfortunately occurred in the United States. In this article, the authors outline the historical discoveries that led from kuru to the identification and isolation of the pathological prion proteins in addition to providing a brief description of human prion diseases and iatrogenic forms of CJD, a brief history of prion disease nosocomial transmission, and a summary of the CDC and WHO guidelines for prevention of prion disease transmission and decontamination of prion-contaminated neurosurgical instruments.
Topics: Animal Diseases; Animals; Cattle; Creutzfeldt-Jakob Syndrome; Cross Infection; History, 20th Century; History, 21st Century; Humans; Iatrogenic Disease; Neurosurgical Procedures; Prion Diseases
PubMed: 27364252
DOI: 10.3171/2016.5.FOCUS15126 -
Veterinary Research Oct 2023The emergence of bovine spongiform encephalopathy (BSE) prions from atypical scrapie has been recently observed upon experimental transmission to rodent and swine...
The emergence of bovine spongiform encephalopathy (BSE) prions from atypical scrapie has been recently observed upon experimental transmission to rodent and swine models. This study aimed to assess whether the inoculation of atypical scrapie could induce BSE-like disease in cattle. Four calves were intracerebrally challenged with atypical scrapie. Animals were euthanized without clinical signs of prion disease and tested negative for PrP accumulation by immunohistochemistry and western blotting. However, an emergence of BSE-like prion seeding activity was detected during in vitro propagation of brain samples from the inoculated animals. These findings suggest that atypical scrapie may represent a potential source of BSE infection in cattle.
Topics: Sheep; Female; Cattle; Animals; Swine; Prions; Encephalopathy, Bovine Spongiform; Scrapie; Prion Diseases; Brain; Cattle Diseases; Sheep Diseases; Swine Diseases
PubMed: 37794450
DOI: 10.1186/s13567-023-01225-2 -
Folia Neuropathologica 2012The transmissible spongiform encephalopathies (TSEs), or prion diseases, are a group of neurodegenerative disorders which include kuru, Creutzfeldt-Jakob disease (CJD),... (Review)
Review
The transmissible spongiform encephalopathies (TSEs), or prion diseases, are a group of neurodegenerative disorders which include kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker (GSS) syndrome, and fatal familial insomnia in men, natural scrapie in sheep, goats and mufflons, transmissible mink encephalopathy in ranch-reared mink, chronic wasting disease of mule deer and elk, bovine spongiform encephalopathy or "mad cow disease" and its analogues in several exotic species of antelopes and wild felids in zoological gardens, and feline spongiform encephalopathy in domestic cats. This short review summarizes the history of the research to find the nature of the scrapie agent, especially as I have witnessed it unfolding before my eyes. I review the historical background of TSEs starting from the first description of scrapie in 1732. In 1957, the first prion disease in humans, kuru was described and its transmissibility was demonstrated in 1965 by seminal work of Gajdusek, Gibbs and colleagues, followed by transmission of CJD and then, GSS. In 1982, Stanley B. Prusiner formulated "prion hypothesis" which has dominated the field for the last 30 years. This theory had been recently extended to cover other neurodegenerations which are caused by misfolded proteins; these disease are called prionoids.
Topics: Animals; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Prion Diseases
PubMed: 22505359
DOI: No ID Found -
Neurology Oct 2021Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of human prion disease and typically occurs in middle to late life. sCJD in early adulthood is...
BACKGROUND AND OBJECTIVES
Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of human prion disease and typically occurs in middle to late life. sCJD in early adulthood is extremely uncommon. The purpose of this report is to raise awareness of cases of sCJD in young patients that are not associated with a genetic mutation or acquired prion disease risk factors.
METHODS
We describe the clinical presentation, diagnostic workup, and postmortem examination of a 22-year-old man with sCJD.
RESULTS
The patient presented with a rapidly progressive neurocognitive disorder consisting of early and prominent psychiatric symptoms. CSF real-time quaking-induced conversion (RT-QuIC) was indeterminate, and brain MRI was suggestive of prion disease. Neuropathologic examination and the absence of a genetic mutation and acquired prion disease risk factors resulted in a final diagnosis of sCJD.
CONCLUSION
Although extremely rare, sCJD can occur in young people and should be considered in the setting of rapidly progressive neuropsychiatric conditions. Postmortem examination is required to diagnose the type of prion disease and remains important to surveil for known and potentially novel acquired prion diseases.
Topics: Adolescent; Adult; Autopsy; Brain; Creutzfeldt-Jakob Syndrome; Humans; Magnetic Resonance Imaging; Male; Prion Diseases; Young Adult
PubMed: 34497065
DOI: 10.1212/WNL.0000000000012737 -
Mammalian Genome : Official Journal of... Jun 2009Prion diseases are transmissible neurodegenerative disorders of mammalian species and include scrapie, bovine spongiform encephalopathy (BSE), and variant...
Prion diseases are transmissible neurodegenerative disorders of mammalian species and include scrapie, bovine spongiform encephalopathy (BSE), and variant Creutzfeldt-Jakob disease (vCJD). The prion protein (PrP) plays a key role in the disease, with coding polymorphism in both human and mouse influencing disease susceptibility and incubation time, respectively. Other genes are also thought to be important and a plausible candidate is Sprn, which encodes the PrP-like protein Shadoo (Sho). Sho is expressed in the adult central nervous system and exhibits neuroprotective activity reminiscent of PrP in an in vitro assay. To investigate the role of Sprn in prion disease incubation time we sequenced the open reading frame (ORF) in a diverse panel of mice and saw little variation except in strains derived from wild-trapped mice. Sequencing the untranslated regions revealed polymorphisms that allowed us to carry out an association study of incubation period in the Northport heterogeneous stock of mice inoculated with Chandler/RML prions. We also examined the expression level of Sprn mRNA in the brains of normal and prion-infected mice and saw no correlation with either genotype or incubation time. We therefore conclude that Sprn does not play a major role in prion disease incubation time in these strains of mice.
Topics: Animals; Cell Cycle Proteins; Genotype; Mice; Open Reading Frames; Polymorphism, Single Nucleotide; Prion Diseases; Rodent Diseases; Time Factors
PubMed: 19513788
DOI: 10.1007/s00335-009-9194-5 -
CMAJ : Canadian Medical Association... Nov 1997By biological and medical criteria, prions are infectious agents; however, many of their properties differ profoundly from those of conventional microbes. Prions are... (Review)
Review
By biological and medical criteria, prions are infectious agents; however, many of their properties differ profoundly from those of conventional microbes. Prions are "encoded" by alterations in protein conformation rather than in nucleic acid or amino acid sequence. New epidemic prion diseases (bovine spongiform encephalopathy and new variant Creutzfeldt-Jakob disease) have recently emerged under the active surveillance of the modern world. The risk of contracting prion disease from blood products or other biologicals is now a focus of worldwide concern. Much has been discovered about prions and prion diseases, but much remains to be done.
Topics: Global Health; Humans; Prion Diseases; Prions; Risk Factors; Transfusion Reaction; United Kingdom
PubMed: 9371069
DOI: No ID Found -
Biochimica Et Biophysica Acta Jul 2006The family of transmissible spongiform encephalopathies (TSE), also termed prion diseases, is a group of fatal, neurodegenerative diseases characterized by the... (Review)
Review
The family of transmissible spongiform encephalopathies (TSE), also termed prion diseases, is a group of fatal, neurodegenerative diseases characterized by the accumulation of a misfolded protein, the disease-associated prion protein PrPSc. This glycoprotein differs in secondary structure from its normal, cellular isoform PrPC, which is physiologically expressed mostly by neurons. Scrapie is a prion disease first described in the 18th century in sheep and goats, and has been established as a model in rodents to study the pathogenesis and pathology of prion diseases. Assuming a multitude of molecular parameters change in the tissue in the course of the disease, FTIR microspectroscopy has been proposed as a valuable new method to study and identify prion-affected tissues due to its ability to detect a variety of changes in molecular structure and composition simultaneously. This paper reviews and discusses results from previous FTIR microspectroscopic studies on nervous tissue of scrapie-infected hamsters in the context of histological and molecular alterations known from conventional pathogenesis studies. In particular, data from studies reporting on disease-specific changes of protein structure characteristics, and also results of a recent study on hamster dorsal root ganglia (DRG) are discussed. These data include an illustration on how the application of a brilliant IR synchrotron light source enables the in situ investigation of localized changes in protein structure and composition in nervous cells or tissue due to PrPSc deposition, and a demonstration on how the IR spectral information can be correlated with results of complementary studies using immunohistochemistry and x-ray fluorescence techniques. Using IR microspectroscopy, some neurons exhibited a high accumulation of disease-associated prion protein evidenced by an increased amount of beta-sheet at narrow regions in or around the infected nervous cells. However, not all neurons from terminally diseased hamsters showed PrPSc deposition. Generally, the average spectral differences between all control and diseased DRG spectra are small but consistent as demonstrated by independent experiments. Along with studies on the purified misfolded prion protein, these data suggest that synchrotron FTIR microspectroscopy is capable of detecting the misfolded prion protein in situ without the necessity of immunostaining or purification procedures.
Topics: Animals; Cats; Cattle; Cricetinae; Nervous System; Prion Diseases; Prions; Scrapie; Spectroscopy, Fourier Transform Infrared
PubMed: 16887095
DOI: 10.1016/j.bbamem.2006.05.026 -
Viruses Sep 2021Genetic prion disease accounts for 10-15% of prion disease. While insertion of four or more octapeptide repeats are clearly pathogenic, smaller repeat insertions have an...
Genetic prion disease accounts for 10-15% of prion disease. While insertion of four or more octapeptide repeats are clearly pathogenic, smaller repeat insertions have an unclear pathogenicity. The goal of this case series was to provide an insight into the characteristics of the 2-octapeptide repeat genetic variant and to provide insight into the risk for Creutzfeldt-Jakob disease in asymptomatic carriers. 2-octapeptide repeat insertion prion disease cases were collected from the National Prion Disease Pathology Surveillance Center (US), the National Prion Clinic (UK), and the National Creutzfeldt-Jakob Disease Registry (Australia). Three largescale population genetic databases were queried for the 2-octapeptide repeat insertion allele. Eight cases of 2-octapeptide repeat insertion were identified. The cases were indistinguishable from the sporadic Creutzfeldt-Jakob cases of the same molecular subtype. Western blot characterization of the prion protein in the absence of enzymatic digestion with proteinase K revealed that 2-octapeptide repeat insertion and sporadic Creutzfeldt-Jakob disease have distinct prion protein profiles. Interrogation of large-scale population datasets suggested the variant is of very low penetrance. The 2-octapeptide repeat insertion is at most a low-risk genetic variant. Predictive genetic testing for asymptomatic blood relatives is not likely to be justified given the low risk.
Topics: Aged; Aged, 80 and over; Alleles; Brain; Creutzfeldt-Jakob Syndrome; Female; Humans; Male; Methionine; Middle Aged; Mutagenesis, Insertional; Oligopeptides; Prion Diseases; Prion Proteins; Prions
PubMed: 34578375
DOI: 10.3390/v13091794