scholarly journals INTERRELATION OF PRIONS WITH NON-CODING RNAS

2018 ◽  
Vol 22 (4) ◽  
pp. 415-424
Author(s):  
R. N. Mustafin ◽  
E. K. Khusnutdinova
Keyword(s):  
Prion Diseases ◽  
Noncoding Rnas ◽  
Transmissible Spongiform Encephalopathies ◽  
Regulatory Effect ◽  
Spongiform Encephalopathies ◽  
Neuronal Stem Cells ◽  
Non Coding Rnas ◽  
The Brain ◽  
Brain Tissues

Prions are alternative infectious conformations for some cellular proteins. For the protein PrPC(PrP – prion protein, С – common), a prion conformation, called PrPSc(S – scrapie), is pathological. For example, in mammals the PrPScprion causes transmissible spongiform encephalopathies accumulating in the brain tissues of PrPScaggregates that have amyloid properties. MicroRNAs and long non-coding RNAs can be translated into functional peptides. These peptides can have a regulatory effect on genes from which their non-coding RNAs are transcribed. It has been assumed that prions, like peptides, due to the presence of specific domains, can also activate certain non-coding RNAs. Some of the activated non-coding RNAs can catalyze the formation of new prions from normal protein, playing their role in the pathogenesis of prion diseases. Confirmation of this assumption is the presence of the association of alleles of microRNA with the development of the disease, which indicates the role of the specific sequences of noncoding RNAs in the catalysis of prion formation. In the brain tissues of patients with prion diseases, as well as in exosomes containing an abnormal PrPScisoform, changes in the levels of microRNA have been observed. A possible cause is the interaction of the spatial domains of PrPScwith the sequences of the non-coding RNA genes, which causes a change in their expression. MicroRNAs, in turn, affect the synthesis of long non-coding RNAs. We hypothesize that long noncoding RNAs and possibly microRNAs can interact with PrPCcatalyzing its transformation into PrPSc. As a result, the number of PrPScincreases exponentially. In the brain of animals and humans, transposon activity has been observed, which has a regulatory effect on the differentiation of neuronal stem cells. Transposons form the basis of domain structures of long non-coding RNAs. In addition, they are important sources of microRNA. Since prion diseases can arise as sporadic and hereditary cases, and hereditary predisposition is important for the development of pathology, we hypothesize the role of individual features of activation of transposons in the pathogenesis of prion diseases. The activation of transposons in the brain at certain stages of development, as well as under the influence of stress, is reflected in the peculiarities of expression of specific non-coding RNAs that are capable of catalyzing the transition of the PrPCprotein to PrPSc. Research in this direction can be the basis for targeted anti-microRNA therapy of prion diseases.

Prions: Protein Aggregation and Infectious Diseases

2009 ◽  
Vol 89 (4) ◽  
pp. 1105-1152 ◽  
Author(s):  
Adriano Aguzzi ◽  
Anna Maria Calella
Keyword(s):  
Protein Aggregation ◽  
Prion Diseases ◽  
Physiological Role ◽  
Infectious Agent ◽  
Normal Function ◽  
Cellular Prion Protein ◽  
Transmissible Spongiform Encephalopathies ◽  
Pathological Features ◽  
Spongiform Encephalopathies

Transmissible spongiform encephalopathies (TSEs) are inevitably lethal neurodegenerative diseases that affect humans and a large variety of animals. The infectious agent responsible for TSEs is the prion, an abnormally folded and aggregated protein that propagates itself by imposing its conformation onto the cellular prion protein (PrPC) of the host. PrPCis necessary for prion replication and for prion-induced neurodegeneration, yet the proximal causes of neuronal injury and death are still poorly understood. Prion toxicity may arise from the interference with the normal function of PrPC, and therefore, understanding the physiological role of PrPCmay help to clarify the mechanism underlying prion diseases. Here we discuss the evolution of the prion concept and how prion-like mechanisms may apply to other protein aggregation diseases. We describe the clinical and the pathological features of the prion diseases in human and animals, the events occurring during neuroinvasion, and the possible scenarios underlying brain damage. Finally, we discuss potential antiprion therapies and current developments in the realm of prion diagnostics.

Trace elements and prion diseases: a review of the interactions of copper, manganese and zinc with the prion protein

2006 ◽  
Vol 7 (1-2) ◽  
pp. 97-105 ◽  
Author(s):  
Scott P. Leach ◽  
M. D. Salman ◽  
Dwayne Hamar
Keyword(s):  
Trace Elements ◽  
Prion Protein ◽  
Copper Ions ◽  
Prion Diseases ◽  
Normal Function ◽  
Transmissible Spongiform Encephalopathies ◽  
Copper Binding ◽  
Spongiform Encephalopathies ◽  
Copper Manganese ◽  
The Brain

Transmissible spongiform encephalopathies (TSEs) are a family of neurodegenerative diseases characterized by their long incubation periods, progressive neurological changes, and spongiform appearance in the brain. There is much evidence to show that TSEs are caused by an isoform of the normal cellular surface prion protein PrPC. The normal function of PrPC is still unknown, but it exhibits properties of a cupro-protein, capable of binding up to six copper ions. There are two differing views on copper's role in prion diseases. While one view looks at the PrPC copper-binding as the trigger for conversion to PrPSc, the opposing viewpoint sees a lack of PrPC copper-binding resulting in the conformational change into the disease causing isoform. Manganese and zinc have been shown to interact with PrPC as well and have been found in abnormal levels in prion diseases. This review addresses the interaction between select trace elements and the PrPC.

scholarly journals Transmissible Spongiform Encephalopathies Affecting Humans

2013 ◽  
Vol 2013 ◽  
pp. 1-11
Author(s):  
Dudhatra G. B. ◽  
Avinash Kumar ◽  
Modi C. M. ◽  
Awale M. M. ◽  
Patel H. B. ◽  
...  
Keyword(s):  
Neurological Disease ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathies ◽  
Neurologic Diseases ◽  
Abnormal Protein ◽  
Chain Reactions ◽  
Personality Changes ◽  
Incubation Periods ◽  
The Brain

Transmissible spongiform encephalopathies (TSEs) or prion diseases are group of rare and rapidly progressive fatal neurologic diseases. The agents responsible for human prion diseases are abnormal proteins or prion that can trigger chain reactions causing normal proteins in the brain to change to the abnormal protein. These abnormal proteins are resistant to enzymatic breakdown, and they accumulate in the brain, leading to damage. TSEs have long incubation periods followed by chronic neurological disease and fatal outcomes, have similar pathology limited to the CNS including convulsions, dementia, ataxia, and behavioral or personality changes, and are experimentally transmissible to some other species.

scholarly journals Mechanisms of prion-induced neurodegeneration

2016 ◽  
Vol 18 ◽  
Author(s):  
Paula Saá ◽  
David A. Harris ◽  
Larisa Cervenakova
Keyword(s):  
Neurodegenerative Disorders ◽  
Protein Misfolding ◽  
Prion Diseases ◽  
Neuronal Loss ◽  
Cellular Prion Protein ◽  
Transmissible Spongiform Encephalopathies ◽  
Therapeutic Approaches ◽  
Spongiform Encephalopathies ◽  
Membrane Bound ◽  
The Brain

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal neurodegenerative disorders characterised by long incubation period, short clinical duration, and transmissibility to susceptible species. Neuronal loss, spongiform changes, gliosis and the accumulation in the brain of the misfolded version of a membrane-bound cellular prion protein (PrPC), termed PrPTSE, are diagnostic markers of these diseases. Compelling evidence links protein misfolding and its accumulation with neurodegenerative changes. Accordingly, several mechanisms of prion-mediated neurotoxicity have been proposed. In this paper, we provide an overview of the recent knowledge on the mechanisms of neuropathogenesis, the neurotoxic PrP species and the possible therapeutic approaches to treat these devastating disorders.

Human prion diseases

2010 ◽  
pp. 5023-5032
Author(s):  
R G Will
Keyword(s):  
Prion Protein ◽  
Prion Diseases ◽  
Mammalian Species ◽  
Normal Function ◽  
Transmissible Spongiform Encephalopathies ◽  
Neuronal Dysfunction ◽  
Spongiform Encephalopathies ◽  
Protease Digestion ◽  
Incubation Periods ◽  
The Brain

Prion protein (for proteinacious infectious particle) is a membrane-associated glycoprotein present in all mammalian species. Its normal function is unknown, but in prion diseases (also known as transmissible spongiform encephalopathies) a post-translationally modified form of the protein, partially resistant to protease digestion, is deposited in the brain and associated—after long incubation periods—with neuronal dysfunction and death....

Prion protein allotype profiling by mass spectrometry

2003 ◽  
Vol 75 (2-3) ◽  
pp. 317-323 ◽  
Author(s):  
M. E. Schininà ◽  
Bruno Maras ◽  
Franco Cardone ◽  
Carmine Mancone ◽  
S. Principe ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Prion Diseases ◽  
Laboratory Animals ◽  
Transmissible Spongiform Encephalopathies ◽  
Fragment Composition ◽  
Spongiform Encephalopathies ◽  
Optimized Protocol ◽  
Genotype Composition ◽  
The Central Nervous System ◽  
The Brain

Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative pathologies characterized by the formation in the central nervous system of the amyloid protein PrPSc, which derives from a cellular precursor called PrPc. Epidemiological and laboratory studies have shown that in species where the PrPc gene is polymorphic, the genotype composition is an important factor for the development of the disease. Identification of PrPSc allotypes accumulated in the brain during the disease proved valuable to investigate whether these polymorphisms are critical for the pathological conversion. These analyses are complicated by the heterogeneity and the insolubility of the prion amyloid extracted from affected brains, which have been obviated by extensive digestion of extracted fractions and analysis of peptide fragment composition. We have developed an optimized protocol of liquid chromatography/mass spectrometry (LC/MS) that can reliably map PrP peptides in digested fractions with a low PrPSc/contaminants ratio. This approach has been successfully applied to the analysis of amyloidogenesis in experimentally infected PrP-heterozygous laboratory animals.

scholarly journals The Role of the Nasal Cavity in the Pathogenesis of Prion Diseases

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2287
Author(s):  
Anthony E. Kincaid
Keyword(s):  
Central Nervous System ◽  
Nasal Cavity ◽  
Medical Devices ◽  
Animal Species ◽  
Prion Proteins ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathies ◽  
The Central Nervous System

Prion diseases, or transmissible spongiform encephalopathies (TSEs), are a class of fatal neurodegenerative diseases caused by the entry and spread of infectious prion proteins (PrPSc) in the central nervous system (CNS). These diseases are endemic to certain mammalian animal species that use their sense of smell for a variety of purposes and therefore expose their nasal cavity (NC) to PrPSc in the environment. Prion diseases that affect humans are either inherited due to a mutation of the gene that encodes the prion protein, acquired by exposure to contaminated tissues or medical devices, or develop without a known cause (referred to as sporadic). The purpose of this review is to identify components of the NC that are involved in prion transport and to summarize the evidence that the NC serves as a route of entry (centripetal spread) and/or a source of shedding (centrifugal spread) of PrPSc, and thus plays a role in the pathogenesis of the TSEs.

Metallic prions

2004 ◽  
Vol 71 ◽  
pp. 193-202 ◽  
Author(s):  
David R Brown
Keyword(s):  
Prion Protein ◽  
Binding Capacity ◽  
Normal Function ◽  
Transmissible Spongiform Encephalopathies ◽  
Published Data ◽  
Normal Brain ◽  
Copper Binding ◽  
Loss Of Function ◽  
Spongiform Encephalopathies ◽  
The Brain

Prion diseases, also referred to as transmissible spongiform encephalopathies, are characterized by the deposition of an abnormal isoform of the prion protein in the brain. However, this aggregated, fibrillar, amyloid protein, termed PrPSc, is an altered conformer of a normal brain glycoprotein, PrPc. Understanding the nature of the normal cellular isoform of the prion protein is considered essential to understanding the conversion process that generates PrPSc. To this end much work has focused on elucidation of the normal function and activity of PrPc. Substantial evidence supports the notion that PrPc is a copper-binding protein. In conversion to the abnormal isoform, this Cu-binding activity is lost. Instead, there are some suggestions that the protein might bind other metals such as Mn or Zn. PrPc functions currently under investigation include the possibility that the protein is involved in signal transduction, cell adhesion, Cu transport and resistance to oxidative stress. Of these possibilities, only a role in Cu transport and its action as an antioxidant take into consideration PrPc's Cu-binding capacity. There are also more published data supporting these two functions. There is strong evidence that during the course of prion disease, there is a loss of function of the prion protein. This manifests as a change in metal balance in the brain and other organs and substantial oxidative damage throughout the brain. Thus prions and metals have become tightly linked in the quest to understand the nature of transmissible spongiform encephalopathies.

Sign in / Sign up

Export Citation Format

Share Document