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Prion Diseases

Eirini Kanata, Ewa Golanska, Anna Villar-Piqué, Aikaterini Karsanidou, Dimitra Dafou, Konstantinos Xanthopoulos, Matthias Schmitz, Isidro Ferrer, André Karch, Beata Sikorska, Pawel P Liberski, Theodoros Sklaviadis, Inga Zerr, Franc Llorens
Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of human prion disease. It is invariably fatal and displays a short clinical disease stage. The key event in sCJD is the propagation of a beta-sheet rich conformer of the physiological PrPC protein, known as PrPSc . Neuropathological disease characteristics include gliosis, neuronal loss and spongiform degeneration; disease clinical manifestations refer to mental and visual disabilities, cognitive impairment, gait or limb ataxia, myoclonus and mutism...
October 8, 2018: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Daniela Sarnataro
The misfolding and aggregation of proteins is the neuropathological hallmark for numerous diseases including Alzheimer's disease, Parkinson's disease, and prion diseases. It is believed that misfolded and abnormal β-sheets forms of wild-type proteins are the vectors of these diseases by acting as seeds for the aggregation of endogenous proteins. Cellular prion protein (PrPC ) is a glycosyl-phosphatidyl-inositol (GPI) anchored glycoprotein that is able to misfold to a pathogenic isoform PrPSc , the causative agent of prion diseases which present as sporadic, dominantly inherited and transmissible infectious disorders...
October 9, 2018: International Journal of Molecular Sciences
Nuška Čakš Jager, Mara Popović, Mateja Blaško Markič, Alenka Kraigher
Introduction: The objective was to present the results of surveillance of prion diseases in Slovenia that was established in 1996 and then to assess the interdisciplinary approach according to the algorithm of case management and reporting data to the National Register at the National Institute of Public Health. Methods: A descriptive study of Creutzfeldt-Jakob disease (CJD) recorded in the period from 1996 to 2017 was carried out. Results: A total of 123 cases of prion disease were notified between 1996 and 2017...
December 2018: Zdravstveno Varstvo
Ji-Hong Moon, Jae-Kyo Jeong, Jeong-Min Hong, Jae-Won Seol, Sang-Youel Park
Accumulation of prion protein (PrPc) into a protease-resistant form (PrPsc) in the brains of humans and animals affects the central nervous system. PrPsc occurs only in mammals with transmissible prion diseases. Prion protein refers to either the infectious pathogen itself or the main component of the pathogen. Recent studies suggest that autophagy is one of the major functions that keep cells alive and which has a protective effect against neurodegeneration. In this study, we investigated whether the anti-hypertensive drug, captopril, could attenuate prion peptide PrP (106-126)-induced calcium alteration-mediated neurotoxicity...
October 5, 2018: Molecular Neurobiology
Elaheh Ekhtiari Bidhendi, Johan Bergh, Per Zetterström, Karin Forsberg, Bente Pakkenberg, Peter M Andersen, Stefan L Marklund, Thomas Brännström
Motor neurons containing aggregates of superoxide dismutase 1 (SOD1) are hallmarks of amyotrophic lateral sclerosis (ALS) caused by mutations in the gene encoding SOD1. We have previously reported that two strains of mutant human (h) SOD1 aggregates (denoted A and B) can arise in hSOD1-transgenic models for ALS and that inoculation of such aggregates into the lumbar spinal cord of mice results in rostrally spreading, templated hSOD1 aggregation and premature fatal ALS-like disease. Here, we explored whether mutant hSOD1 aggregates with prion-like properties also exist in human ALS...
October 3, 2018: Acta Neuropathologica
Alison J E Green
The diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) can be difficult, but the real-time quaking-induced conversion (RT-QuIC) assays have made a considerable impact on its clinical diagnosis. This technique exploits the ability of the misfolded pathological form of prion protein (PrPSc ) found in cerebrospinal fluid (CSF) to induce conversion of normal PrP to the misfolded form, which subsequently aggregates. The formation of these aggregates of misfolded PrP is monitored in real time using fluorescent dyes...
October 3, 2018: Practical Neurology
Alba Marín-Moreno, Patricia Aguilar-Calvo, José Luis Pitarch, Juan Carlos Espinosa, Juan María Torres
Co-occurrence of different prion strains into the same host has been recognized as a natural phenomenon for several sporadic Creutzfeldt-Jakob disease (sCJD) patients and natural scrapie cases. The final outcome of prion co-infection is not easily predictable. In addition to the usual factors that influence prion conversion, the replication of one strain may entail positive or negative consequences to the other.The main aim of this study was to gain insights into the prion co-infection and interference concepts and their potential therapeutic implications...
October 3, 2018: Journal of Virology
Roger A Moore, Anne Ward, Brent Race, Suzette A Priola
Prions represent a class of universally fatal and transmissible neurodegenerative disorders that affect humans and other mammals. The prion agent contains a pathologically aggregated form of the host prion protein that can transmit infectivity without any bacterial or viral component and is thus difficult to inactivate using disinfection protocols designed for infectious microorganisms. Methods for prion inactivation include treatment with acids, bases, detergents, bleach, prolonged autoclaving and incineration...
November 2018: Biochimica et biophysica acta. Proteins and proteomics
Yingjun Liu, Silvia Sorce, Mario Nuvolone, Julie Domange, Adriano Aguzzi
Prion diseases, Alzheimer's disease and Parkinson's disease (PD) are fatal degenerative disorders that share common neuropathological and biochemical features, including the aggregation of pathological protein conformers. Lymphocyte activation gene 3 (Lag3, also known as CD223) is a member of the immunoglobulin superfamily of receptors expressed on peripheral immune cells, microglia and neurons, which serves as a receptor for α-synuclein aggregates in PD. Here we examined the possible role of Lag3 in the pathogenesis of prion diseases...
October 2, 2018: Scientific Reports
Grace I Hallinan, Aleksandra P Pitera, Prutha Patel, Jonathan West, Katrin Deinhardt
Neurofibrillary tangles, formed of hyperphosphorylated, misfolded tau accumulations, are a pathological hallmark of neurodegenerative diseases such as Alzheimer's disease (AD) and frontotemporal dementia. The neuroanatomical localisation of tau pathology in AD brains of different disease stages suggests that tau tangle pathology is spreading throughout the brain along connected neuronal circuits. Pathogenic tau can act as a prion-like seed, inducing the misfolding of native tau and leading to disease propagation throughout the brain...
September 29, 2018: Journal of Neuroscience Methods
Qiuye Li, Fei Wang, Xiangzhu Xiao, Chae Kim, Jen Bohon, Janna Kiselar, Jiri G Safar, Jiyan Ma, Witold K Surewicz
Prion diseases are neurodegenerative disorders that affect many mammalian species. Mammalian prion proteins (PrPs) can misfold into many different aggregates. However, only a small subpopulation of these structures is infectious. One of the major unresolved questions in prion research is identifying which specific structural features of these misfolded protein aggregates are important for prion infectivity in vivo Previously, two types of proteinase K-resistant, self-propagating aggregates were generated from the recombinant mouse prion protein in the presence of identical cofactors...
October 1, 2018: Journal of Biological Chemistry
Kevin Mullane, Michael Williams
Compounds targeted for the treatment of Alzheimer's Disease (AD) have consistently failed in clinical trials despite evidence for target engagement and pharmacodynamic activity. This questions the relevance of compounds acting at current AD drug targets - the majority of which reflect the seminal amyloid and, to a far lesser extent, tau hypotheses - and limitations in understanding AD causality as distinct from general dementia. The preeminence of amyloid and tau led to many alternative approaches to AD therapeutics being ignored or underfunded to the extent that their causal versus contributory role in AD remains unknown...
September 28, 2018: Biochemical Pharmacology
Marco Bardelli, Karl Frontzek, Luca Simonelli, Simone Hornemann, Mattia Pedotti, Federica Mazzola, Manfredi Carta, Valeria Eckhardt, Rocco D'Antuono, Tommaso Virgilio, Santiago F González, Adriano Aguzzi, Luca Varani
Antibodies to the prion protein, PrP, represent a promising therapeutic approach against prion diseases but the neurotoxicity of certain anti-PrP antibodies has caused concern. Here we describe scPOM-bi, a bispecific antibody designed to function as a molecular prion tweezer. scPOM-bi combines the complementarity-determining regions of the neurotoxic antibody POM1 and the neuroprotective POM2, which bind the globular domain (GD) and flexible tail (FT) respectively. We found that scPOM-bi confers protection to prion-infected organotypic cerebellar slices even when prion pathology is already conspicuous...
October 2018: PLoS Pathogens
Li-Juan Wang, Xiao-Dan Gu, Guo-Hua Yu, Liang Shen, Hong-Fang Ji
Prion diseases are characterized by the conformational conversion of the cellular prion protein (PrPC ) to the pathogenic isoform (PrPSc ). Lipids have been found to interact with PrPC and contribute to the efficient formation of PrPSc . Non-mammalian PrPs are not readily to undergo the conversion process into an infectious isoform, yet the effect of lipid on the conformational conversion of non-mammalian PrPC remains to be explored. Herein, the effects of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) on full-length recombinant chicken PrP (ChPrP) 24-249 and murine PrP (MoPrP) 23-230 were investigated...
October 2018: Veterinary Microbiology
Harish Kumar, Jayant B Udgaonkar
The spread and deposition of infectious fibrillar protein aggregates in the brain via a prion-like mechanism is a critical component in the patho-physiology of various neurodegenerative diseases, including the tauopathies. In tauopathies, two isoforms of tau, containing three and four microtubule binding repeats, are found to aggregate, and the type of isoform present in aggregates determines the type of tauopathy. Cross-seeding between the two tau isoforms is limited by an asymmetric barrier similar to the species barrier that restricts prion transmission across species, whose origin has remained unclear...
September 26, 2018: Journal of Molecular Biology
Hubert Aviolat, Yves Nominé, Sophie Gioria, Anna Bonhoure, David Hoffmann, Christine Ruhlmann, Hélène Nierengarten, Frank Ruffenach, Pascal Villa, Yvon Trottier, Fabrice A C Klein
Numerous proteins can coalesce into amyloid self-assemblies, which are responsible for a class of diseases called amyloidoses, but which can also fulfill important biological functions and are of great interest for biotechnology. Amyloid aggregation is a complex multi-step process, poorly prone to detailed structural studies. Therefore, small molecules interacting with amyloids are often used as tools to probe the amyloid aggregation pathway, and in some cases to treat amyloidoses as they prevent pathogenic protein aggregation...
September 25, 2018: Journal of Molecular Biology
Kristiana Xhima, Fadl Nabbouh, Kullervo Hynynen, Isabelle Aubert, Anurag Tandon
BACKGROUND: The characteristic progression of Lewy pathology in Parkinson's disease likely involves intercellular exchange and the accumulation of misfolded α-synuclein amplified by a prion-like self-templating mechanism. Silencing of the α-synuclein gene could provide long-lasting disease-modifying benefits by reducing the requisite substrate for the spreading aggregation. OBJECTIVES: As a result of the poor penetration of viral vectors across the blood-brain barrier, gene therapy for central nervous system disorders requires direct injections into the affected brain regions, and invasiveness is further increased by the need for bilateral delivery to multiple brain regions...
September 28, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
Muhammet Uslupehlivan, Remziye Deveci, Cemal Ün
The prion protein is a membrane-bound glycoprotein which consists mainly α-helix structure. In contrast, the infectious prion protein shows the beta-sheet structure. The prion-associated diseases are all lethal neurodegenerative abnormalities, called transmissible spongiform encephalopathies. Scrapie is the most common type of these illnesses affecting sheep, goats, and moufflon. The VRQ, AHQ, ARR and N146S polymorphisms in the sheep prion gene have been found to be associated with resistance to scrapie disease...
September 24, 2018: Molecular and Cellular Probes
Rumana Akhter
Circular RNAs (circRNAs) represent a special group of noncoding single-stranded highly stable ribonucleic acid entities abundant in the eukaryotic transcriptome. These circular forms of RNAs are significantly enriched in human brain and retinal tissues. However, the biological evolution and function of these circRNAs are poorly understood. Recent reports showed circRNA to be an important player in the development of neurodegenerative diseases like Alzheimer's disease. With the progression of age, circRNA level increases in the brain and also in age-associated neurological disorder like Alzheimer's disease (AD), Parkinson's disease, inflammatory neuropathy, nervous system neoplasms, and prion diseases...
2018: Advances in Experimental Medicine and Biology
Mathias Jucker, Lary C Walker
Many neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are characterized by the progressive appearance of abnormal proteinaceous assemblies in the nervous system. Studies in experimental systems indicate that the assemblies originate from the prion-like seeded aggregation of specific misfolded proteins that proliferate and amass to form the intracellular and/or extracellular lesions typical of each disorder. The host in which the proteopathic seeds arise provides the biochemical and physiological environment that either supports or restricts their emergence, proliferation, self-assembly, and spread...
October 2018: Nature Neuroscience
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