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Cell and Tissue Research Apr 2023The properties of infectious prions and the pathology of the diseases they cause are dependent upon the unique conformation of each prion strain. How the pathology of... (Review)
Review
The properties of infectious prions and the pathology of the diseases they cause are dependent upon the unique conformation of each prion strain. How the pathology of prion disease correlates with different strains and genetic backgrounds has been investigated via in vivo assays, but how interactions between specific prion strains and cell types contribute to the pathology of prion disease has been dissected more effectively using in vitro cell lines. Observations made through in vivo and in vitro assays have informed each other with regard to not only how genetic variation influences prion properties, but also how infectious prions are taken up by cells, modified by cellular processes and propagated, and the cellular components they rely on for persistent infection. These studies suggest that persistent cellular infection results from a balance between prion propagation and degradation. This balance may be shifted depending upon how different cell lines process infectious prions, potentially altering prion stability, and how fast they can be transported to the lysosome. Thus, in vitro studies have given us a deeper understanding of the interactions between different prions and cell types and how they may influence prion disease phenotypes in vivo.
Topics: Humans; Prions; Prion Diseases; Cell Line
PubMed: 35107622
DOI: 10.1007/s00441-021-03572-y -
Handbook of Clinical Neurology 2018Prion diseases (e.g., Creutzfeldt-Jakob disease) are rapidly progressive neurodegenerative diseases that are invariably fatal. Diagnosing prion disease can be difficult... (Review)
Review
Prion diseases (e.g., Creutzfeldt-Jakob disease) are rapidly progressive neurodegenerative diseases that are invariably fatal. Diagnosing prion disease can be difficult and can lead to frustration. There is no currently available disease-altering treatment for prion diseases and the care and management of affected patients are directed towards symptomatic relief and quality of life. In this chapter, we highlight the many unique challenges of prion disease and how they affect care and management strategies. Symptomatic treatment follows many of the same principles observed in geriatric and/or hospice care, with some important differences due to disease-specific characteristics. We provide an overview of pharmacologic and nonpharmacologic strategies for managing symptoms of prion disease. Education and psychosocial support are also very important in managing patients and families affected by the illness and are discussed in detail. Readers of this chapter will understand the context of caring for a patient with prion disease and will be supplied with practical tools for managing symptoms and educating other healthcare personnel and caregivers. Additional resources for assistance in the care of prion disease patients are also discussed.
Topics: Creutzfeldt-Jakob Syndrome; Humans; Patient Care Management; Quality of Life
PubMed: 29887147
DOI: 10.1016/B978-0-444-63945-5.00021-0 -
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 -
Viruses Dec 2018Prion diseases display multiple disease phenotypes characterized by diverse clinical symptoms, different brain regions affected by the disease, distinct cell tropism and... (Review)
Review
Prion diseases display multiple disease phenotypes characterized by diverse clinical symptoms, different brain regions affected by the disease, distinct cell tropism and diverse PrP deposition patterns. The diversity of disease phenotypes within the same host is attributed to the ability of PrP to acquire multiple, alternative, conformationally distinct, self-replicating PrP states referred to as prion strains or subtypes. Structural diversity of PrP strains has been well documented, yet the question of how different PrP 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 PrP, are important players in defining strain-specific structures and disease phenotypes. This article introduces a new hypothesis, according to which individual strain-specific PrP structures govern selection of PrP sialoglycoforms that form strain-specific patterns of carbohydrate epitopes on PrP surface and contribute to defining the disease phenotype and outcomes.
Topics: Glycosylation; Models, Molecular; N-Acetylneuraminic Acid; Phenotype; Polysaccharides; Prion Diseases; Prions
PubMed: 30567302
DOI: 10.3390/v10120723 -
Molecular Neurobiology Jun 2022Serpins represent the most broadly distributed superfamily of proteases inhibitors. They contribute to a variety of physiological functions and any alteration of the...
Serpins represent the most broadly distributed superfamily of proteases inhibitors. They contribute to a variety of physiological functions and any alteration of the serpin-protease equilibrium can lead to severe consequences. SERPINA3 dysregulation has been associated with Alzheimer's disease (AD) and prion diseases. In this study, we investigated the differential expression of serpin superfamily members in neurodegenerative diseases. SERPIN expression was analyzed in human frontal cortex samples from cases of sporadic Creutzfeldt-Jakob disease (sCJD), patients at early stages of AD-related pathology, and age-matched controls not affected by neurodegenerative disorders. In addition, we studied whether Serpin expression was dysregulated in two animal models of prion disease and AD.Our analysis revealed that, besides the already observed upregulation of SERPINA3 in patients with prion disease and AD, SERPINB1, SERPINB6, SERPING1, SERPINH1, and SERPINI1 were dysregulated in sCJD individuals compared to controls, while only SERPINB1 was upregulated in AD patients. Furthermore, we analyzed whether other serpin members were differentially expressed in prion-infected mice compared to controls and, together with SerpinA3n, SerpinF2 increased levels were observed. Interestingly, SerpinA3n transcript and protein were upregulated in a mouse model of AD. The SERPINA3/SerpinA3nincreased anti-protease activity found in post-mortem brain tissue of AD and prion disease samples suggest its involvement in the neurodegenerative processes. A SERPINA3/SerpinA3n role in neurodegenerative disease-related protein aggregation was further corroborated by in vitro SerpinA3n-dependent prion accumulation changes. Our results indicate SERPINA3/SerpinA3n is a potential therapeutic target for the treatment of prion and prion-like neurodegenerative diseases.
Topics: Acute-Phase Proteins; Alzheimer Disease; Animals; Brain; Creutzfeldt-Jakob Syndrome; Humans; Mice; Neurodegenerative Diseases; Prion Diseases; Prions; Serpins
PubMed: 35416570
DOI: 10.1007/s12035-022-02817-3 -
International Journal of Molecular... Jun 2022Prion diseases are a group of devastating neurodegenerative disorders, which include Creutzfeldt-Jakob disease (CJD) in humans, and scrapie and bovine spongiform...
Prion diseases are a group of devastating neurodegenerative disorders, which include Creutzfeldt-Jakob disease (CJD) in humans, and scrapie and bovine spongiform encephalopathy (BSE) in animals [...].
Topics: Animals; Brain; Cattle; Creutzfeldt-Jakob Syndrome; Encephalopathy, Bovine Spongiform; Prion Diseases; Prions; Scrapie; Sheep
PubMed: 35742934
DOI: 10.3390/ijms23126490 -
Communicable Diseases Intelligence... Jun 2023Nationwide surveillance of Creutzfeldt-Jakob disease (CJD) and other human prion diseases is performed by the Australian National Creutzfeldt-Jakob Disease Registry...
Nationwide surveillance of Creutzfeldt-Jakob disease (CJD) and other human prion diseases is performed by the Australian National Creutzfeldt-Jakob Disease Registry (ANCJDR). National surveillance encompasses the period since 1 January 1970, with prospective surveillance occurring from 1 October 1993. Over this prospective surveillance period, considerable developments have occurred in pre-mortem diagnostics; in the delineation of new disease subtypes; and in a heightened awareness of prion diseases in healthcare settings. Surveillance practices of the ANCJDR have evolved and adapted accordingly. This report summarises the activities of the ANCJDR during 2022. Since the ANCJDR began offering diagnostic cerebrospinal fluid (CSF) 14-3-3 protein testing in Australia in September 1997, the annual number of referrals has steadily increased. In 2022, a total of 599 domestic CSF specimens were referred for diagnostic testing and 79 persons with suspected human prion disease were formally added to the national register. As of 31 December 2022, just under half of the 79 suspect case notifications (36/79) remain classified as 'incomplete'; 15 cases were classified as 'definite' and 23 as 'probable' prion disease; five cases were excluded through neuropathological examination. For 2022, fifty-five percent of all suspected human-prion-disease-related deaths in Australia underwent neuropathological examination. No cases of variant or iatrogenic CJD were identified. The SARS-CoV-2 pandemic did not affect prion disease surveillance outcomes in Australia during 2022.
Topics: Humans; Creutzfeldt-Jakob Syndrome; Prospective Studies; Disease Notification; Australia; COVID-19; SARS-CoV-2; Prion Diseases
PubMed: 37357180
DOI: 10.33321/cdi.2023.47.37 -
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 -
Expert Opinion on Therapeutic Patents Dec 2021: Prion diseases are a class of rare and fatal neurodegenerative diseases for which no cure is currently available. They are characterized by conformational conversion... (Review)
Review
: Prion diseases are a class of rare and fatal neurodegenerative diseases for which no cure is currently available. They are characterized by conformational conversion of cellular prion protein (PrP) into the disease-associated 'scrapie' isoform (PrP). Under an etiological point of view, prion diseases can be divided into acquired, genetic, and idiopathic form, the latter of which are the most frequent.: Therapeutic approaches targeting prion diseases are based on the use of chemical and nature-based compounds, targeting either PrP or PrP or other putative player in pathogenic mechanism. Other proposed anti-prion treatments include passive and active immunization strategies, peptides, aptamers, and PrP-directed RNA interference techniques. The treatment efficacy has been mainly assessed in cell lines or animal models of the disease testing their ability to reduce prion accumulation.: The assessed strategies focussing on the identification of an efficient anti-prion therapy faced various issues, which go from permeation of the blood brain barrier to immunological tolerance of the host. Indeed, the use of combinatory approaches, which could boost a synergistic anti-prion effect and lower the potential side effects of single treatments and may represent an extreme powerful and feasible way to tackle prion disease.
Topics: Animals; Humans; Patents as Topic; PrPC Proteins; PrPSc Proteins; Prion Diseases
PubMed: 34134584
DOI: 10.1080/13543776.2021.1945033 -
Current Issues in Molecular Biology 2020Incidences of iatrogenic Creutzfeldt-Jakob disease (iCJD) are caused by transplantation of prion-contaminated hormones, cornea and dura mater as well as contact with...
Incidences of iatrogenic Creutzfeldt-Jakob disease (iCJD) are caused by transplantation of prion-contaminated hormones, cornea and dura mater as well as contact with prion- contaminated medical devices, such as stereotactic electrodes, used in neurosurgery. Because prions are highly resistant and difficult to inactivate, prion contamination is a severe risk when medical instruments are reused after surgical procedures involving suspicious and confirmed cases of patients with prion diseases. Therefore, when high-risk procedures such as cerebral surgery, craniotomy surgery, orthopaedic spinal surgery and ophthalmic surgery are performed for high-risk patients or individuals with prion diseases, it is neces- sary to appropriately treat the medical devices using scientifically proven prion inactivation methods. In this chapter, we introduce fundamental aspects of prion inactivation methods, looking specifically at the practical issues involved in their implementation.
Topics: Animals; Detergents; Humans; Prion Diseases; Prions; Risk Factors; Surgical Equipment
PubMed: 31507270
DOI: 10.21775/cimb.036.023