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Journal of the American Dental... Nov 2003Prion diseases are a group of rare fatal neurodegenerative disorders in humans and animals that are histopathologically characterized by spongiform change within the... (Review)
Review
BACKGROUND
Prion diseases are a group of rare fatal neurodegenerative disorders in humans and animals that are histopathologically characterized by spongiform change within the central nervous system.
TYPES OF STUDIES REVIEWED
The author reviewed all available case reports and any studies of the oral aspects of prion diseases published in peer-reviewed journals and available via PubMed. He then outlined the risk of nosocomial transmission of prions in dental health care.
RESULTS
Sporadic Creutzfeldt-Jakob disease, or sCJD, is the most common of the acquired human prion disorders, and it typically affects elderly people and leads to rapid death. In contrast, variant CJD, or vCJD, has affected young adults from Europe, giving rise to a slow onset disorder comprising both psychiatric and neurological upset. Oral neurological manifestations are rare and seem to occur only in people with vCJD; there are no oral mucosal or gingival manifestations of prion disease. Prions can be detected in the oral tissues--usually the gingivae and dental pulp--of animals experimentally infected with prions. In contrast, prions have not been detected in the pulpal tissue of people with sCJD, and there are no data of pulpal infection in vCJD. There also are no data suggesting that prions are transmitted easily in the dental setting, but there remains the rare risk of such transmission if appropriate infection control measures are not adhered to.
CLINICAL IMPLICATIONS
Few people in the United States and worldwide have prion disease. Oral manifestations are rare. Evidence suggests that the risk of transmission and acquisition of a prion infection as a result of dental treatment is rare, if appropriate infection control measures are maintained.
Topics: Adult; Aged; Animals; Creutzfeldt-Jakob Syndrome; Cross Infection; Dental Care; Humans; Infection Control, Dental; Prion Diseases; Prions; Risk Factors
PubMed: 14664268
DOI: 10.14219/jada.archive.2003.0079 -
British Journal of Hospital Medicine
Review
Topics: Animals; Humans; Incidence; Prion Diseases; Zoonoses
PubMed: 8832037
DOI: No ID Found -
Current Pharmaceutical Biotechnology Apr 2005An infectious particle, termed prion, composed largely and perhaps solely of a single protein, is the likely causative agent of prion disease. It produces lethal decline... (Review)
Review
An infectious particle, termed prion, composed largely and perhaps solely of a single protein, is the likely causative agent of prion disease. It produces lethal decline of cognitive and motor function. The responsible protein arrives at a pathogenic state by misfolding from a normal form that has ubiquitous tissue distribution. Prion diseases are often called spongiform encephalopathies. Probably most mammalian species develop these diseases. Specific examples in various animals are -Scrapie, Transmissible Mink Encephalopathy (TME ), Chronic Wasting Disease(CWD) and bovine spongiform encephalopathy (BSE). Humans are also susceptible to several prion diseases: Creutzfeld-Jacob Disease (CJD), Gerstmann-Straussler-Scheinker Syndrome (GSS), Fatal Familial Insomnia (FFI), Kuru and Alpers Syndrome. This paper reviews transmission of this diseases, protein involvement, nature of protein, the conversion process from PrP(c) to PrP(Sc), conversion of prion protein in vitro, the different proposed models for the conversion of PrP(c) to PrP(Sc), prion and other amyloid diseases, prion strains, structure of PrP(c) the particular process that may induce prion disease, and immunization against these diseases.
Topics: Animals; Brain; Humans; Prion Diseases; Prions; Protein Folding; Structure-Activity Relationship
PubMed: 15853695
DOI: 10.2174/1389201053642321 -
Journal of Endodontics Oct 2008The aim of this article was to provide the dental community with a brief overview of the characteristics, risk of transmission, and the infection-control implications of... (Review)
Review
The aim of this article was to provide the dental community with a brief overview of the characteristics, risk of transmission, and the infection-control implications of prions in dentistry. MEDLINE, EMBASE, CINAHL, The Cochrane Library, and relevant databases were searched, and a targeted internet search was conducted up to July 2007. Transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative diseases that are rapidly progressive and always fatal, with no approved cure, and their definite diagnosis can only be obtained at post mortem autopsy. The causative agent, prion protein, resists conventional sterilization methods especially when infected tissue becomes dried onto glass or metal surfaces. To date, there are no reported definite or suspected cases of disease transmission arising from dental procedures, and there seems to be no correlation between dental treatment and TSEs. Because there is a theoretical but real risk of transmission of prion disease from dental instruments (although it is extremely low, especially in North America), as a general rule, appropriate family and medical history (including the risk for prion diseases) should be obtained from all patients, before all dental procedures. TSE research regarding diagnosis, transmission, treatment, and inactivation of prions and other transmissible amyloidoses are ongoing, and, thus, dental professionals should maintain optimal and up-to-date standards of knowledge, infection control, and decontamination.
Topics: Creutzfeldt-Jakob Syndrome; Dental Care; Humans; Infection Control, Dental; Mouth Diseases; Prion Diseases; Prions; Risk Factors; Sterilization
PubMed: 18793912
DOI: 10.1016/j.joen.2008.07.008 -
International Journal of Molecular... Oct 2020Prion diseases are a unique group of infectious chronic neurodegenerative disorders to which there are no cures. Although prion infections do not stimulate adaptive... (Review)
Review
Prion diseases are a unique group of infectious chronic neurodegenerative disorders to which there are no cures. Although prion infections do not stimulate adaptive immune responses in infected individuals, the actions of certain immune cell populations can have a significant impact on disease pathogenesis. After infection, the targeting of peripherally-acquired prions to specific immune cells in the secondary lymphoid organs (SLO), such as the lymph nodes and spleen, is essential for the efficient transmission of disease to the brain. Once the prions reach the brain, interactions with other immune cell populations can provide either host protection or accelerate the neurodegeneration. In this review, we provide a detailed account of how factors such as inflammation, ageing and pathogen co-infection can affect prion disease pathogenesis and susceptibility. For example, we discuss how changes to the abundance, function and activation status of specific immune cell populations can affect the transmission of prion diseases by peripheral routes. We also describe how the effects of systemic inflammation on certain glial cell subsets in the brains of infected individuals can accelerate the neurodegeneration. A detailed understanding of the factors that affect prion disease transmission and pathogenesis is essential for the development of novel intervention strategies.
Topics: Aging; Brain; Disease Susceptibility; Humans; Immune System; Immunomodulation; Prion Diseases; Prions
PubMed: 33023255
DOI: 10.3390/ijms21197299 -
Acta Biochimica Et Biophysica Sinica Jul 2014The hallmark of prion disease is the accumulation of misfolded protein PrP(Sc), which is toxic to neuronal cells. The proteasome system is responsible for the rapid,... (Review)
Review
The hallmark of prion disease is the accumulation of misfolded protein PrP(Sc), which is toxic to neuronal cells. The proteasome system is responsible for the rapid, precise, and timely degradation of proteins and plays an important role in cellular protein quality control. Increasing evidence indicates impaired activity of proteasomes in prion diseases. Accumulated PrP(Sc) can directly or indirectly affect proteasome activity. Misfolded protein may influence the assembly and activity of 19S regulatory particle, or post-translational modification of 20S proteasome, which may adversely affect the protein degradation activity of proteasomes. In this review, we summarized the recent findings concerning the possible regulation of proteasomes in prion and other neurodegenerative diseases. The proteasome system may enhance its degradation activity by changing its structure, and this activity can also be increased by related chaperones when neuronal cells are subject to stress. When the proteasome system is inhibited, degradation of protein aggregates via autophagy may increase as a compensatory system. It is possible that a balance exists between the proteasome and autophagy in vivo; when one is impaired, the activity of the other may increase to maintain homeostasis. However, more studies are needed to elucidate the relationship between the proteasome system and autophagy.
Topics: Autophagy; Humans; Neurodegenerative Diseases; Prion Diseases; Proteasome Endopeptidase Complex; Ubiquitin
PubMed: 24829398
DOI: 10.1093/abbs/gmu031 -
Molecular Aspects of Medicine Apr 2018Over the past decade, small extracellular vesicles called exosomes have been observed to harbour protein and genetic cargo that can assist in health and also cause... (Review)
Review
Over the past decade, small extracellular vesicles called exosomes have been observed to harbour protein and genetic cargo that can assist in health and also cause disease. Many groups are extensively investigating the mechanisms involved that regulate the trafficking and packaging of exosomal contents and how these processes may be deregulated in disease. Prion diseases are transmissible neurodegenerative disorders and are characterized by the presence of detectable misfolded prion proteins. The disease associated form of the prion protein can be found in exosomes and its transmissible properties have provided a reliable experimental read out that can be used to understand how exosomes and their cargo are involved in cell-cell communication and in the spread of prion diseases. This review reports on the current understanding of how exosomes are involved in the intercellular spread of infectious prions. Furthermore, we discuss how these principles are leading future investigations in developing new exosome based diagnostic tools and therapeutic drugs that could be applied to other neurodegenerative diseases.
Topics: Animals; Biomarkers; Cell Communication; Disease Susceptibility; Exosomes; Humans; Neurodegenerative Diseases; Prion Diseases; Prion Proteins; Prions; Protein Transport
PubMed: 29196098
DOI: 10.1016/j.mam.2017.11.011 -
Current Opinion in Pharmacology Feb 2019
Topics: Animals; Clinical Trials as Topic; Drug Discovery; Humans; Prion Diseases
PubMed: 31186145
DOI: 10.1016/j.coph.2019.05.002 -
JAMA Network Open Oct 2020Human prion disease surveillance is critical to detect possible cases of variant Creutzfeldt-Jakob disease and other acquired forms of prion disease in the United...
IMPORTANCE
Human prion disease surveillance is critical to detect possible cases of variant Creutzfeldt-Jakob disease and other acquired forms of prion disease in the United States. Results are presented here that describe 12 years of surveillance in Washington, the only US state that has reported the presence of classic bovine spongiform encephalopathy, an animal prion disease that has been shown to transmit to humans.
OBJECTIVE
To describe the current prion disease surveillance system in Washington and the epidemiological and clinical results of surveillance from 2006 through 2017.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study reports findings from the human prion disease surveillance system in place in Washington state from January 1, 2006, through December 31, 2017. Participants included Washington residents with a clinical suspicion of human prion disease or suggestive test results from the National Prion Disease Pathology Surveillance Center or with prion disease listed as a cause of death on the death certificate. Data for this report were analyzed from June 1, 2016, to July 1, 2020.
EXPOSURE
Human prion disease diagnosis.
MAIN OUTCOMES AND MEASURES
The main outcome was incidence of human prion disease cases, including identification of variant Creutzfeldt-Jakob disease.
RESULTS
A total of 143 human prion disease cases were detected during the study period, none of which met criteria for a variant Creutzfeldt-Jakob disease diagnosis. Among 137 definite or probable cases, 123 (89.8%) occurred in persons aged 55 years or older, with a median age at death of 66 years (range, 38-84 years). Most patients were White (124 [92.5%] among 134 with reported race), and slightly over half were male (70 [51.1%]). The average annual age-adjusted prion disease incidence was 1.5 per million population per year, slightly higher than the national rate of 1.2 per million. A total of 99 cases (69.2%) were confirmed by neuropathology. Sporadic prion disease was the most common diagnosis, in 134 cases (93.7%), followed by familial prion disease in 8 cases (5.6%). One iatrogenic prion disease case (0.7%) was also reported.
CONCLUSIONS AND RELEVANCE
The findings of this cross-sectional study suggest that demographic characteristics of patients with prion disease in Washington are consistent with national findings. The slightly higher incidence rate may be due to the state's enhanced surveillance activities, including close collaboration with key partners and educational efforts targeted toward health care providers. Results indicate that surveillance will continue to be beneficial for monitoring epidemiological trends, facilitating accurate diagnoses, and detecting variant Creutzfeldt-Jakob disease or other emerging human prion disease cases.
Topics: Adult; Aged; Aged, 80 and over; Animals; Cattle; Creutzfeldt-Jakob Syndrome; Cross-Sectional Studies; Humans; Incidence; Male; Middle Aged; Population Surveillance; Prion Diseases; Washington
PubMed: 33064135
DOI: 10.1001/jamanetworkopen.2020.20690 -
Expert Opinion on Investigational Drugs Dec 2020
Topics: Animals; Humans; Mutation; Prion Diseases; Prion Proteins; Research Design
PubMed: 33089731
DOI: 10.1080/13543784.2020.1839048