A5022161083- Prion Diseases and Protein Misfolding
- Neurological diseases and metabolism
- Trace Elements in Health
- Remote Sensing and Land Use
- Advanced Computational Techniques and Applications
- RNA regulation and disease
- Enzyme Structure and Function
- Amino Acid Enzymes and Metabolism
- Milk Quality and Mastitis in Dairy Cows
- Protein Structure and Dynamics
- Microbial infections and disease research
- Amyotrophic Lateral Sclerosis Research
- Alcoholism and Thiamine Deficiency
- HIV Research and Treatment
- Alzheimer's disease research and treatments
- Infectious Diseases and Mycology
- Herpesvirus Infections and Treatments
- Radioactive element chemistry and processing
- Animal Disease Management and Epidemiology
- Genetic Neurodegenerative Diseases
- Cardiac Imaging and Diagnostics
- RNA Research and Splicing
- Neurogenetic and Muscular Disorders Research
- Infectious Encephalopathies and Encephalitis
- Animal Virus Infections Studies
MRC Prion Unit
2013-2024
University College London
2011-2023
Medical Research Council
2001-2023
Animal and Plant Health Agency
2021
National Hospital for Neurology and Neurosurgery
1992-2015
Google (United States)
2015
Institute of Electrical and Electronics Engineers
2013-2014
Universidad de Extremadura
2013-2014
Canadian Standards Association
2014
Marina Del Rey Hospital
2014
Although a functional role in copper binding has been suggested for the prion protein, evidence at affinities characteristic of authentic metal-binding proteins lacking. By presentation copper(II) ions presence weak chelator glycine, we have now characterized two high-affinity sites divalent transition metals within human protein. One is N-terminal octapeptide-repeat segment and K d 10 −14 M, with other (Ni 2+ , Zn Mn ) three or more orders magnitude weakly. However, NMR fluorescence data...
Prion propagation involves the conversion of cellular prion protein (PrP C ) into a disease-specific isomer, PrP Sc , shifting from predominantly α-helical to β-sheet structure. Here, conditions were established in which recombinant human could switch between native α conformation, characteristic and compact, highly soluble, monomeric form rich β The soluble (β-PrP) exhibited partial resistance proteinase K digestion, was direct precursor fibrillar structures closely similar those isolated...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBinding and hydrolysis of nucleotides in the chaperonin catalytic cycle: Implications for mechanism assisted protein foldingGraham S. Jackson, Rosemary A. Staniforth, David J. Halsall, Tony Atkinson, John Holbrook, Anthony R. Clarke, Steven G. BurstonCite this: Biochemistry 1993, 32, 10, 2554–2563Publication Date (Print):March 16, 1993Publication History Published online1 May 2002Published inissue 16 March...
Huntington's disease (HD) causes widespread CNS changes and systemic abnormalities including endocrine immune dysfunction. HD biomarkers are needed to power clinical trials of potential treatments. We used multiplatform proteomic profiling reveal plasma with progression. Proteins interest were evaluated using immunoblotting ELISA in from 2 populations, CSF R6/2 mice. The identified proteins demonstrate neuroinflammation warrant further investigation as possible biomarkers. Keywords: •...
Previous small studies in Aotearoa New Zealand have indicated a high prevalence of gout. This study sought to determine the gout entire population using national-level health data sets.We used hospitalization and drug dispensing claims for allopurinol colchicine from Health Tracker (ANZHT) estimate 2009, stratified by age, gender, ethnicity socio-economic status (n = 4 295 296).were compared with those obtained an independent large primary care set (HealthStat, n 555 313). Results. The...
Acidity constants of the lowest triplet state have been determined for seven aromatic molecules by two independent methods. In first method is populated flash photolysis and acid-base equilibrium studied spectrophotometrically. second difference between acidity in ground states calculated from energy levels acid base derived phosphorescence spectra. For five molecules investigated—2-naphthol, 1- 2-naphthoic acids, 2-naphthyl-amine acridine—acidity are now known three electronic states. It...
Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that specifically affects motor neurons and leads to progressive ultimately fatal loss of function, resulting in death typically within 3 5 years diagnosis. The starts with focal centre weakness, such as one limb, appears spread other parts the body. Mutations superoxide dismutase 1 (SOD1) are known cause it generally accepted they lead pathology not by enzymatic activity but gain some unknown toxic function(s)....
Disease-related PrP(Sc) [pathogenic PrP (prion protein)] is classically distinguished from its normal cellular precursor, PrP(C)(cellular PrP) by detergent insolubility and partial resistance to proteolysis. Although molecular diagnosis of prion disease has historically relied upon detection protease-resistant fragments using PK (proteinase K), it now apparent that a substantial fraction disease-related destroyed this protease. Recently, thermolysin been identified as complementary tool PK,...
Prion infection is characterized by the conversion of host cellular prion protein (PrP(C)) into disease-related conformers (PrP(Sc)) and can be arrested in vivo passive immunization with anti-PrP monoclonal antibodies. Here, we show that ability an antibody to cure prion-infected cells correlates its binding affinity for PrP(C) rather than PrP(Sc). We have visualized this interaction at molecular level determining crystal structure human PrP bound Fab fragment ICSM 18, which has highest...
Isolations of reovirus-like agents (rotaviruses) were made from nine 23 outbreaks piglet diarrhoea on different farms and both weaned unweaned piglets. The viruses shown to be morphologically anti-genically similar the rotaviruses children calves. Gnotobiotig piglets given intranasal inoculations five isolates developed acute gastroenteritis, virus was re-isolated faeces or intestinal contents. not adapted replicate in cell culture. We conclude that pig rotavirus is commonly associated with...
Mutation of the human prion protein gene (PRNP) open reading frame (ORF) accounts for almost all reported familial concurrence disease. The more common mutations globally: octapeptide repeat insertions, P102L, D178N, E200K, and V210I have occurred in large multigenerational pedigrees display autosomal dominant inheritance, however, many rare genetic changes been that are uncertain pathogenicity. Based on 19 years PRNP sequencing at MRC Prion Unit, London, analysis 3664 samples from patients...
A blood-based biomarker of neuronal damage in sporadic Creutzfeldt-Jakob disease (sCJD) will be extremely valuable for both clinical practice and research aiming to develop effective therapies.We used an ultrasensitive immunoassay measure two candidate biomarkers, tau neurofilament light (NfL), serum from patients with sCJD healthy controls. We tested longitudinal sample sets six investigate changes over time, examined correlations rate progression associations known phenotype...
Prion diseases are fatal neurodegenerative conditions with highly accurate CSF and imaging diagnostic tests, but major unmet needs for blood biomarkers. Using ultrasensitive immuno-assays, we measured tau neurofilament light chain (NfL) protein concentrations in 709 plasma samples taken from 377 individuals prion disease during a 12 year prospective clinical study, alongside healthy neurological control groups. This provides an unprecedented opportunity to evaluate their potential as Plasma...
Abstract Human prion diseases are remarkable for long incubation times followed typically by rapid clinical decline. Seed amplification assays and neurodegeneration biofluid biomarkers remarkably useful in the phase, but their potential to predict onset healthy people remains unclear. This is relevant not only design of preventive strategies those at-risk diseases, more broadly, because prion-like mechanisms thought underpin many neurodegenerative disorders. Here, we report accrual a...
Prions, transmissible agents that cause Creutzfeldt-Jakob disease (CJD) and other prion diseases, are known to resist conventional sterilization procedures. Iatrogenic transmission of classical CJD via neurosurgical instruments is well documented the involvement lymphoreticular tissues in variant (vCJD), together with unknown population prevalence asymptomatic vCJD infection, has led concerns about from a wide range surgical To address this problem, conditions were sought destroy PrP(Sc)...
Although the physiological function of prion protein remains unknown, in vitro experiments suggest that may bind copper (II) ions and play a role transport or homoeostasis vivo. The unstructured N-terminal region has been shown to up six ions, with each these co-ordinated by single histidine imidazole nearby backbone amide nitrogen atoms. Individually, sites have micromolar affinities, which is weaker than would be expected true cuproprotein. In present study, we show subsaturating levels...
In prion diseases, the misfolded protein aggregates are derived from cellular (PrP C ). Numerous ligands have been reported to bind human PrP (huPrP), but none structured region with affinity required for a pharmacological chaperone. Using equilibrium dialysis, we screened molecules previously suggested interact discriminate between those which did not PrP, behaved as nonspecific polyionic or formed genuine interaction. Those that could potentially act chaperones. Here report cationic...