Prions
Dongyou Liu in Handbook of Foodborne Diseases, 2018
Scrapie may be the oldest prion disease. The infectious nature of the disease in sheep was postulated as early as the eighteenth century, although its transmissibility was not experimentally proven until 1936 [30]. Scrapie has been reported worldwide and affects most sheep-producing regions except for Australia and New Zealand. However, recent studies have shown that scrapie has two distinct forms, classical and atypical [31]. Cases of atypical scrapie have been reported in Australia and New Zealand [32], where classical scrapie is not found. Similarly, BSE comprises classical BSE (C-type BSE), and two atypical types of the disease, named the H- and L-types [33,34]. In CWD, there are at least two strains including CWD1 and CWD2 [35], while a recent study has shown the presence of more CWD strains [36]. CWD is found in both free and captive populations and has been observed in at least 22 states in the United States and three Canadian provinces [37]. The Republic of Korea recorded CWD in imported elk [38], while CWD-reindeer was found in wild populations of Norway [39].
Methods to Decide Whether or Not an Illness Is Infectious
Johan Giesecke in Modern Infectious Disease Epidemiology, 2017
The sheep disease scrapie has been described since the eighteenth century, and the reasoning in the report went as follows: if scrapie could be transmitted to humans and appear as CJD or a similar condition, then CJD should be more common in populations living near herds of sheep with high prevalence of scrapie. In fact the incidence of CJD is strikingly uniform all over the world; it is a very rare disease with an incidence of about 1 per million population per year. It shows the same incidence in the UK, where scrapie has been endemic for at least 250 years, as in Japan where scrapie is rare and in Australia, where scrapie is non-existent. A French study at the time had also failed to find any association between local scrapie prevalence and CJD incidence in different regions of France.
Scrapie in Britain, 1730–1960
Kiheung Kim in The Social Construction of Disease, 2006
In sum, the whole process of disease recognition was closely associated with the institutionalisation of research on the disease. In particular, the institutional settings of veterinary and agricultural science played an important role in developing the research on scrapie. In the early days, a scrapie-like disease was recognised in terms of local knowledge. Knowledge of the disease was largely embodied in the crafts and practices of local farmers and shepherds. However, with the development of veterinary medicine, scrapie became recognised as an independent disease in sheep. In the first half of the twentieth century, scrapie became one of the main subjects of veterinary study. The whole process of disease recognition was, in fact, closely associated with the development of veterinary medicine.
Ultrasensitive techniques and protein misfolding amplification assays for biomarker-guided reconceptualization of Alzheimer’s and other neurodegenerative diseases
Published in Expert Review of Neurotherapeutics, 2021
Nicole Campese, Maria Francesca Beatino, Claudia Del Gamba, Elisabetta Belli, Linda Giampietri, Eleonora Del Prete, Alessandro Galgani, Andrea Vergallo, Gabriele Siciliano, Roberto Ceravolo, Harald Hampel, Filippo Baldacci
Prions are ‘small proteinaceous infectious particles, which are resistant to inactivation by most procedures that modify nucleic acids’ according to Stanley Prusiner’s definition [27]. First described in the late sixties by Alper and Griffith in their main biochemical and biological features and recognized as the pathogenic agents of scrapie [28–30], prions consist of PrPsc, pathological aggregates of the misfolded Cellular Prion Protein (PrPc) [31]. PrPc may undergo misfolding and aberrant aggregation processes, under still not completely clarified pathophysiological mechanisms, leading to the formation of β-sheet-rich oligomers. These may subsequently promote PrPc misfolding and aggregation into highly ordered protofibrils and fibrils [31]. Protofibrils and fibrils may decay into smaller fragments acting as nucleating agents, inducing further spreading of the aberrant proteins based on sequential nucleation–fragmentation cycles [31].
Membrane insertion and intercellular transfer of glycosylphosphatidylinositol-anchored proteins: potential therapeutic applications
Published in Archives of Physiology and Biochemistry, 2020
However, the conclusion that GPI anchoring of the prion protein favours misfolding of the cellular form into the disease-linked scrapie form as well as the propagation and infectivity of prions seems to be in conflict with recent findings that prion proteins lacking the GPI anchor lead to increased production and spreading of prions in vivo and to a higher risk for the transmission of prion diseases. Compatible with these observations are the thermodynamic characterization and kinetic analysis of the conversion into amyloid fibrils of carboxy-terminally truncated anchor-less forms of prion protein (Kovač et al. 2016). Remarkably, the shortest anchor-less form turned out to be the most labile one in course of temperature increase and to be converted into amyloid fibrils most rapidly upon exposure to acidic pH compared to longer anchor-less forms or full-length GPI-anchored prion protein. Moreover, a difference in length as small as a single amino acid only was reflected in an altered lag time of fibrillization and stability vs. low pH (Kovač et al. 2016). Further detailed experimentation will be required to clarify the contribution of the GPI anchor for the replication and propagation of the scrapie form of prion protein.
The cellular prion protein and its derived fragments in human prion diseases and their role as potential biomarkers
Published in Expert Review of Molecular Diagnostics, 2019
Katrin Thüne, Matthias Schmitz, Anna Villar-Piqué, Hermann Clemens Altmeppen, Markus Schlomm, Saima Zafar, Markus Glatzel, Franc Llorens, Inga Zerr
Prion diseases, also known as transmissible spongiform encephalopathies, are a group of rapidly progressive, currently incurable, and fatal neurodegenerative diseases present in humans and animals. Key neuropathological findings shared by prion diseases and other forms of neurodegenerative conditions, such as Alzheimer`s or Parkinson`s disease, are protein aggregation, widespread neuronal loss, and neuroinflammation [1–3]. The main causative pathogenic event in prion diseases is attributed to changes in the structural conformation of the cellular prion protein (PrPC), resulting in the formation of its pathological isoform PrP Scrapie (PrPSc) in a self-propagating manner [3,4]. The molecular mechanisms that underlie this conversion of PrPC into PrPSc and the evolution of prion diseases remain elusive. Due to the rapidly progressing disease following rather long clinically silent incubation times, the high clinicopathological heterogeneity, and the lack of differentiating markers, early and reliable diagnosis of prion diseases faces significant challenges [5,6]. There is a critical need for the investigation of early pathological alterations that can help to identify early diagnostic markers and to develop novel therapeutic strategies.
Related Knowledge Centers
- Nervous System
- Transmissible Spongiform Encephalopathy
- Prion
- Transgene
- Dystonia
- Bovine Spongiform Encephalopathy
- Meat & Bone Meal
- Specified Risk Material
- Peyer'S Patch
- Small Intestine