Research Topics
Genomes and Genes
| John CollingeSummaryAffiliation: University College London Country: UK Publications
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Detail Information
Publications
The Medical Research Council Prion Disease Rating Scale: a new outcome measure for prion disease therapeutic trials developed and validated using systematic observational studiesAndrew G B Thompson
FRS, MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK
Brain 136:1116-27. 2013..Such approaches may be advantageous in orphan conditions, where single studies of feasible duration will often struggle to achieve statistical power...
Molecular pathology of human prion diseaseJonathan D F Wadsworth
MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK
Acta Neuropathol 121:69-77. 2011..Understanding these relationships will have direct translation to protecting public health...- A clinical study of kuru patients with long incubation periods at the end of the epidemic in Papua New GuineaJohn Collinge
Department of Neurodegenerative Disease, MRC Prion Unit, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
Philos Trans R Soc Lond B Biol Sci 363:3725-39. 2008..Importantly, no evidence for lymphoreticular colonization with prions, seen uniformly in vCJD, was observed in a patient with kuru at tonsil biopsy... - Reminiscences and reflections on kuru, personal and scientificJohn Collinge
MRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
Philos Trans R Soc Lond B Biol Sci 363:3613. 2008 - Review. Lessons of kuru research: background to recent studies with some personal reflectionsJohn Collinge
Department of Neurodegenerative Disease, MRC Prion Unit, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
Philos Trans R Soc Lond B Biol Sci 363:3689-96. 2008..Although now essentially over, the kuru epidemic continues to provide important lessons... - Safety and efficacy of quinacrine in human prion disease (PRION-1 study): a patient-preference trialJohn Collinge
National Prion Clinic, National Hospital for Neurology and Neurosurgery, University College London Hospital National Health Service Foundation Trust, Queen Square, London WC1N 3BG, UK
Lancet Neurol 8:334-44. 2009.... 
Kuru in the 21st century--an acquired human prion disease with very long incubation periodsJohn Collinge
MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, London WC1N 3BG, UK
Lancet 367:2068-74. 2006..We investigated possible incubation periods, pathogenesis, and genetic susceptibility factors in kuru patients in Papua New Guinea...- Molecular neurology of prion diseaseJ Collinge
MRC Prion Unit and National Prion Clinic, Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
J Neurol Neurosurg Psychiatry 76:906-19. 2005.... - A general model of prion strains and their pathogenicityJohn Collinge
MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, London WC1N 3BG, UK
Science 318:930-6. 2007..Recent advances suggest that prions themselves are not directly neurotoxic, but rather their propagation involves production of toxic species, which may be uncoupled from infectivity... - Human prion protein with valine 129 prevents expression of variant CJD phenotypeJonathan D F Wadsworth
Medical Research Council MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
Science 306:1793-6. 2004..Thus, primary and secondary human infection with BSE-derived prions may result in sporadic CJD-like or novel phenotypes in addition to vCJD, depending on the genotype of the prion source and the recipient... - Genetic risk factors for variant Creutzfeldt-Jakob disease: a genome-wide association studySimon Mead
Medical Research Council Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London, UK
Lancet Neurol 8:57-66. 2009.... - The H187R mutation of the human prion protein induces conversion of recombinant prion protein to the PrP(Sc)-like formLaszlo L P Hosszu
MRC Prion Unit, UCL Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London WC1N 3BG, UK
Biochemistry 49:8729-38. 2010..This mutation is distinct from all those associated with GSS, which have much more subtle physical consequences. The degree of instability might be the cause of the unusually early onset of mental disturbance in affected individuals... - Conformational properties of beta-PrPLaszlo L P Hosszu
MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London WC1N 3BG, UK
J Biol Chem 284:21981-90. 2009..This precursor state is almost as compact as the folded PrPC structure and, as it assembles, only residues 126-227 are immobilized within the oligomeric structure, leaving the remainder in a mobile, random-coil state... - Phenotypic heterogeneity in inherited prion disease (P102L) is associated with differential propagation of protease-resistant wild-type and mutant prion proteinJonathan D F Wadsworth
MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery Queen Square, London, UK
Brain 129:1557-69. 2006..Such differential propagation of disease-related isoforms of wild-type PrP and PrP 102L provides a molecular mechanism for generation of the multiple clinicopathological phenotypes seen in inherited prion disease... - Inherited prion disease with six octapeptide repeat insertional mutation--molecular analysis of phenotypic heterogeneitySimon Mead
MRC Prion Unit, Department of Neurodegenerative Diseases, Institute of Neurology, King's College Hospital, London, UK
Brain 129:2297-317. 2006.... - Beta-PrP form of human prion protein stimulates production of monoclonal antibodies to epitope 91-110 that recognise native PrPScAzadeh Khalili-Shirazi
MRC Prion Unit, Department of Neurodegenerative Diseases, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
Biochim Biophys Acta 1774:1438-50. 2007..These results demonstrate strain-dependent variations in chain conformation and packing within the 91-110 region of PrP(Sc)... - Distinct glycoform ratios of protease resistant prion protein associated with PRNP point mutationsAndrew F Hill
MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
Brain 129:676-85. 2006..These data extend the spectrum of recognized PrP(Sc) types seen in human prion diseases and provide further insight into the generation of diverse clinicopathological phenotypes associated with inherited prion disease... - PrP glycoforms are associated in a strain-specific ratio in native PrPScAzadeh Khalili-Shirazi
MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
J Gen Virol 86:2635-44. 2005..These studies are consistent with the view that the proportion of each glycoform incorporated into PrPSc is probably controlled in a strain-specific manner and that each PrPSc particle contains a mixture of glycoforms... - Kuru prions and sporadic Creutzfeldt-Jakob disease prions have equivalent transmission properties in transgenic and wild-type miceJonathan D F Wadsworth
Medical Research Council Prion Unit and Department of Neurodegenerative Disease, University College London Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom
Proc Natl Acad Sci U S A 105:3885-90. 2008..These findings are consistent with the hypothesis that kuru originated from chance consumption of an individual with sporadic CJD... - Identification and characterization of a novel mouse prion gene alleleSarah E Lloyd
MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, London, WC1N 3BG, UK
Mamm Genome 15:383-9. 2004..We conclude that the new allele, Prnp(c), modulates incubation time but not neuropathology and that the previous classification of mice into two distinct groups based on incubation time and Prnp genotype should now be revised... - Molecular and clinical classification of human prion diseaseJonathan D F Wadsworth
MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, London, UK
Br Med Bull 66:241-54. 2003..A molecular classification of human prion diseases seems achievable through characterisation of structural differences of the infectious agent itself... - Codon 129 polymorphism of the human prion protein influences the kinetics of amyloid formationPatrick A Lewis
MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
J Gen Virol 87:2443-9. 2006..However, in a partially denatured conformation, the polymorphic variation has a profound influence on the ability of the protein to form amyloid fibrils spontaneously... - Balancing selection at the prion protein gene consistent with prehistoric kurulike epidemicsSimon Mead
Medical Research Council Prion Unit, and Department of Neurodegenerative Disease, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK
Science 300:640-3. 2003..Worldwide PRNP haplotype diversity and coding allele frequencies suggest that strong balancing selection at this locus occurred during the evolution of modern humans... - Dissociation of pathological and molecular phenotype of variant Creutzfeldt-Jakob disease in transgenic human prion protein 129 heterozygous miceEmmanuel A Asante
Medical Research Council Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom
Proc Natl Acad Sci U S A 103:10759-64. 2006..These data argue that human PRNP 129 heterozygotes will be more susceptible to infection with vCJD prions than to cattle BSE prions and may present with a neuropathological phenotype distinct from vCJD... - Genetic susceptibility, evolution and the kuru epidemicSimon Mead
Department of Neurodegenerative Disease, MRC Prion Unit, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
Philos Trans R Soc Lond B Biol Sci 363:3741-6. 2008..Kuru may have imposed the strongest episode of recent human balancing selection, which may not have been an isolated episode in human history... - HECTD2 is associated with susceptibility to mouse and human prion diseaseSarah E Lloyd
MRC Prion Unit, University College London Institute of Neurology, London, United Kingdom
PLoS Genet 5:e1000383. 2009..Characterisation of such genes is key to understanding human risk and the molecular basis of incubation periods... - Progressive neuronal inclusion formation and axonal degeneration in CHMP2B mutant transgenic miceShabnam Ghazi-Noori
MRC Prion Unit, UCL Institute of Neurology, London WC1N 3BG, UK
Brain 135:819-32. 2012..These data describe the first mouse model of dementia caused by CHMP2B mutation and provide new insights into the mechanisms of CHMP2B-induced neurodegeneration... - Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNPSimon Mead
MRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK
Hum Mol Genet 21:1897-906. 2012..Our data are most consistent with several other risk loci of modest overall effects which will require further genetic association studies to provide definitive evidence... - PRNP allelic series from 19 years of prion protein gene sequencing at the MRC Prion UnitJon A Beck
MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK
Hum Mutat 31:E1551-63. 2010..New genotype-phenotype correlations and population frequencies presented will help the diagnosis and genetic counselling of those with suspected inherited prion disease... - Parietal lobe deficits in frontotemporal lobar degeneration caused by a mutation in the progranulin geneJonathan D Rohrer
Dementia Research Centre, Institute of Neurology, University College London, London, England
Arch Neurol 65:506-13. 2008..To describe the clinical, neuropsychologic, and radiologic features of a family with a C31LfsX35 mutation in the progranulin gene CCDS11483.1)... - Disease-associated prion protein oligomers inhibit the 26S proteasomeMark Kristiansen
MRC Prion Unit, Institute of Neurology, University College London, Queen Square, London, UK
Mol Cell 26:175-88. 2007..Together, these data suggest a mechanism for intracellular neurotoxicity mediated by oligomers of misfolded prion protein... - Inherited prion disease with 4-octapeptide repeat insertion: disease requires the interaction of multiple genetic risk factorsDiego N Kaski
National Prion Clinic, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK
Brain 134:1829-38. 2011..These findings may provide a precedent for understanding apparently sporadic neurodegenerative diseases caused by rare high-risk mutations... - Mapping the progression of progranulin-associated frontotemporal lobar degenerationJonathan D Rohrer
Dementia Research Centre, Institute of Neurology, University College London, London, UK
Nat Clin Pract Neurol 4:455-60. 2008..The patient was initially asymptomatic but developed progressive behavioral and cognitive decline characterized by apathy, impaired emotion recognition, mixed aphasia and parietal lobe dysfunction... - Disease-related prion protein forms aggresomes in neuronal cells leading to caspase activation and apoptosisMark Kristiansen
Medical Research Council Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, United Kingdom
J Biol Chem 280:38851-61. 2005..This, in turn, triggers caspase-dependent apoptosis and further implicates proteasome dysfunction in the pathogenesis of prion diseases... - A distinct clinical, neuropsychological and radiological phenotype is associated with progranulin gene mutations in a large UK seriesJonathan Beck
MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
Brain 131:706-20. 2008..Finally, we confirmed a modifying effect of APOE-E4 genotype on clinical phenotype with a later onset in the GRN carriers suggesting that this gene has distinct phenotypic effects in different neurodegenerative diseases... - Single treatment with RNAi against prion protein rescues early neuronal dysfunction and prolongs survival in mice with prion diseaseMelanie D White
Department of Neurodegenerative Disease, Medical Research Council, Prion Unit Institute of Neurology, University College London, London, United Kingdom
Proc Natl Acad Sci U S A 105:10238-43. 2008.... - Creutzfeldt-Jakob disease, prion protein gene codon 129VV, and a novel PrPSc type in a young British womanSimon Mead
MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
Arch Neurol 64:1780-4. 2007..Modeling studies in transgenic mice suggest that other PRNP genotypes will also be susceptible to infection with bovine spongiform encephalopathy prions but may develop distinctive phenotypes... - Review. The origin of the prion agent of kuru: molecular and biological strain typingJonathan D F Wadsworth
Department of Neurodegenerative Disease, MRC Prion Unit, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
Philos Trans R Soc Lond B Biol Sci 363:3747-53. 2008..Here, we review these findings and discuss how peripheral routes of infection and other factors may be critical modifiers of the kuru phenotype... - Detection of prion infection in variant Creutzfeldt-Jakob disease: a blood-based assayJulie Ann Edgeworth
MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK
Lancet 377:487-93. 2011..We aimed to establish the sensitivity and specificity of a blood-based assay for detection of vCJD prion infection... - Definable equilibrium states in the folding of human prion proteinLaszlo L P Hosszu
MRC Prion Unit and National Prion Clinic, Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
Biochemistry 44:16649-57. 2005..Residual structure within this state is extensive and encompasses the majority of the secondary structure elements found in the native state of the protein... - Absence of spontaneous disease and comparative prion susceptibility of transgenic mice expressing mutant human prion proteinsEmmanuel A Asante
MRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
J Gen Virol 90:546-58. 2009..These data indicate that P102L or E200K mutations of human PrP have differing effects on prion propagation that depend upon prion strain type and can be significantly influenced by mismatch at the polymorphic residue 129... - Tau, prions and Aβ: the triad of neurodegenerationLilla Reiniger
Division of Neuropathology, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, WC1N 3BG, London, UK
Acta Neuropathol 121:5-20. 2011..This includes the novel finding that tau phosphorylation consistently occurs in sporadic CJD, in the absence of amyloid plaques... - Targeting cellular prion protein reverses early cognitive deficits and neurophysiological dysfunction in prion-infected miceGiovanna R Mallucci
MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom
Neuron 53:325-35. 2007..These data suggest that early intervention in human prion disease may lead to recovery of cognitive and behavioral symptoms... - Analysis of 2000 consecutive UK tonsillectomy specimens for disease-related prion proteinAdam Frosh
MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
Lancet 364:1260-2. 2004..Nevertheless, our findings establish a protocol for prevalence screening on a national scale... - Effect of fixation on brain and lymphoreticular vCJD prions and bioassay of key positive specimens from a retrospective vCJD prevalence studyJonathan D F Wadsworth
MRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
J Pathol 223:511-8. 2011..In this context, the Hilton et al study should continue to inform risk assessment pending the outcome of larger-scale studies on discarded surgical tissues and autopsy samples... - Isolation of proteinase K-sensitive prions using pronase E and phosphotungstic acidLaura D'Castro
MRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, United Kingdom
PLoS ONE 5:e15679. 2010..This procedure now allows characterization of proteinase K-sensitive prions and investigation of their clinical relevance in human and animal prion disease without being confounded by contaminating PrP(C)... - Spontaneous generation of mammalian prionsJulie A Edgeworth
Medical Research Council Prion Unit, Department of Neurodegenerative Disease, University College London Institute of Neurology, London WC1N 3BG, United Kingdom
Proc Natl Acad Sci U S A 107:14402-6. 2010..Alternatively, if prions were naturally present in the brain at levels not detectable by conventional methods, metal surfaces might concentrate them to the extent that they become quantifiable by the scrapie cell assay... - Superoxide dismutase 1 and tgSOD1 mouse spinal cord seed fibrils, suggesting a propagative cell death mechanism in amyotrophic lateral sclerosisRuth Chia
Department of Neurodegenerative Disease, University College London Institute of Neurology, London, United Kingdom
PLoS ONE 5:e10627. 2010..Although different mutations lead to varying tendencies of SOD1 to aggregate, we suggest abnormal proteins share a common misfolding pathway that leads to the formation of amyloid fibrils... - A Copine family member, Cpne8, is a candidate quantitative trait gene for prion disease incubation time in mouseSarah E Lloyd
Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, UK
Neurogenetics 11:185-91. 2010..We also show that Cpne8 mRNA is upregulated at the terminal stage of disease, supporting a role in prion disease. Applying these techniques to other loci will facilitate the identification of key pathways in prion disease pathogenesis... - Prion propagation and toxicity in vivo occur in two distinct mechanistic phasesMalin K Sandberg
MRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK
Nature 470:540-2. 2011..Production of neurotoxic species is triggered when prion propagation saturates, leading to a switch from autocatalytic production of infectivity (phase 1) to a toxic (phase 2) pathway... - Detection and characterization of proteinase K-sensitive disease-related prion protein with thermolysinSabrina Cronier
MRC Prion Unit and Department of Neurodegenerative Disease, University College London Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N3BG, UK
Biochem J 416:297-305. 2008..Detection of PK-sensitive isoforms of disease-related PrP using thermolysin should be useful for improving diagnostic sensitivity in human prion diseases... - Subclinical prion infection in humans and animalsAndrew F Hill
MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, London, UK
Br Med Bull 66:161-70. 2003..Subclinical as well as preclinical/clinical prion disease may be relevant when analysing the risk to public health of potential sources of prion exposure... - Characterization of two distinct prion strains derived from bovine spongiform encephalopathy transmissions to inbred miceSarah E Lloyd
MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, London WC1N 3BG, UK
J Gen Virol 85:2471-8. 2004..It is possible that multiple disease phenotypes may also be possible in BSE prion infection in humans and other animals... - The residue 129 polymorphism in human prion protein does not confer susceptibility to Creutzfeldt-Jakob disease by altering the structure or global stability of PrPCLaszlo L P Hosszu
Medical Research Council Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, United Kingdom
J Biol Chem 279:28515-21. 2004..We infer that the M/V effect is mediated through the conformation or stability of disease-related PrP (PrP(Sc)) or intermediates or on the kinetics of their formation... - Recombinant prion protein does not possess SOD-1 activitySamantha Jones
MRC Prion Unit, Department of Neurodegenerative Diseases, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
Biochem J 392:309-12. 2005..Thus if PrP has any role in oxidative stress, it must be indirect as a regulator of protective cellular responses... - Molecular diagnosis of human prion diseaseJonathan D F Wadsworth
MRC Prion Unit, University College London Institute of Neurology, London, UK
Methods Mol Biol 459:197-227. 2008.... - HECTD2, a candidate susceptibility gene for Alzheimer's disease on 10qSarah E Lloyd
MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK
BMC Med Genet 10:90. 2009..In this study we test whether the HECTD2 susceptibility allele seen in prion disease is also implicated in LOAD... - Protein conformation significantly influences immune responses to prion proteinAzadeh Khalili-Shirazi
Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, United Kingdom
J Immunol 174:3256-63. 2005..These differences may be exploitable diagnostically and therapeutically for prion diseases, such as variant Creutzfeldt-Jakob disease... - Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt-Jakob disease associated with blood transfusion: a case reportStephen J Wroe
National Prion Clinic, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
Lancet 368:2061-7. 2006..Tonsil biopsy will allow early and pre-symptomatic diagnosis in other iatrogenically exposed individuals at high risk, as in those with primary infection with bovine spongiform encephalopathy prions... - Magnetization transfer ratio may be a surrogate of spongiform change in human prion diseasesDurrenajaf Siddique
Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
Brain 133:3058-68. 2010..The magnetic resonance imaging measurement of magnetization transfer ratios may be an in vivo surrogate for spongiform change and has potential utility as a therapeutic biomarker in human prion disease... - Inhibition of proteinase K activity by copper(II) ionsLisa A Stone
MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, U K
Biochemistry 46:245-52. 2007..Under these conditions, the apparent resistance of PrPC to proteolysis by PK appears to be directly attributable to the inhibition of PK activity by copper(II) ions... - Investigation of mcp1 as a quantitative trait gene for prion disease incubation time in mouseMarie O'Shea
Medical Research Council Prion Unit and Department of Neurodegenerative Diseases, Institute of Neurology, University College, London WC1N 3BG, United Kingdom
Genetics 180:559-66. 2008..In these models loss of Mcp1 did not show an increase in incubation time suggesting that the effects of Mcp1 may be specific to the ME7 prion strain and that Mcp1 does not contribute to the QTL described on Mmu11... - Folding kinetics of the human prion protein probed by temperature jumpTanya Hart
Medical Research Council Prion Unit, Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom
Proc Natl Acad Sci U S A 106:5651-6. 2009..It is notable that in inherited forms of human prion disease, where point mutations produce a lethal dominant condition, 20 of the 33 amino acid replacements occur in the helix-2/3 sequence... - An enzyme-detergent method for effective prion decontamination of surgical steelGraham S Jackson
MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
J Gen Virol 86:869-78. 2005..The prion-degrading reagents identified in this study are readily available, inexpensive, non-corrosive to instruments, non-hazardous to staff and compatible with current equipment and procedures used in hospital sterilization units... - Pathogenic human prion protein rescues PrP null phenotype in transgenic miceEmmanuel A Asante
MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
Neurosci Lett 360:33-6. 2004..Using the AHP as a marker for PrP function, we conclude that this pathogenic PrP mutation, does not significantly affect the normal neuronal function of PrP... - Removal of the glycosylphosphatidylinositol anchor from PrP(Sc) by cathepsin D does not reduce prion infectivityPatrick A Lewis
MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
Biochem J 395:443-8. 2006..These results show that the GPI anchor has little or no role in either the propagation of PrP(Sc) or on prion infectivity... - Identification of genetic loci affecting mouse-adapted bovine spongiform encephalopathy incubation time in miceSarah E Lloyd
MRC Prion Unit, Department of Neurodegenerative Diseases, Institute of Neurology, University College, London, W21N 3BG, UK
Neurogenetics 4:77-81. 2002..This provides hope that it may be possible to identify human quantitative trait loci for prion incubation time using mouse models that may allow identification of at-risk individuals and the discovery of novel therapeutic targets... - Depleting neuronal PrP in prion infection prevents disease and reverses spongiosisGiovanna Mallucci
Medical Research Council Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London WC1, UK
Science 302:871-4. 2003..Thus, the propagation of nonneuronal PrPSc is not pathogenic, but arresting the continued conversion of PrPc to PrPSc within neurons during scrapie infection prevents prion neurotoxicity... - Species-barrier-independent prion replication in apparently resistant speciesAndrew F Hill
Department of Neurodegenerative Diseases, Institute of Neurology, University College London, UK
APMIS 110:44-53. 2002..Here the issue of subclinical prion diseases is reviewed and implications are discussed... - Shadoo (Sprn) and prion disease incubation time in miceSarah E Lloyd
MRC Prion Unit and Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, UK
Mamm Genome 20:367-74. 2009..We therefore conclude that Sprn does not play a major role in prion disease incubation time in these strains of mice... - A novel exon 2 I27V VCP variant is associated with dissimilar clinical syndromesJonathan D Rohrer
Dementia Research Centre, Institute of Neurology, Queen Square, London, WC1N 3BG, UK
J Neurol 258:1494-6. 2011..Together these cases suggest a potential for the same VCP mutation to produce distinct patterns of brain damage, underlining the clinical heterogeneity of VCP-associated disease... - Chronic wasting disease prions are not transmissible to transgenic mice overexpressing human prion proteinMalin K Sandberg
MRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
J Gen Virol 91:2651-7. 2010..However, it is possible that CWD may be caused by multiple prion strains. Further studies will be required to evaluate the transmission properties of distinct cervid prion strains as they are characterized... - Mortuary rites of the South Fore and kuruJerome T Whitfield
MRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
Philos Trans R Soc Lond B Biol Sci 363:3721-4. 2008..The exclusion of alternative routes of transmission is of importance owing to the dietary exposure of the UK and other populations to bovine spongiform encephalopathy prions... - BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion proteinEmmanuel A Asante
MRC Prion Unit, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK
EMBO J 21:6358-66. 2002..These data suggest that more than one BSE-derived prion strain might infect humans; it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure... - A novel presenilin 1 deletion (p.L166del) associated with early onset familial Alzheimer's diseaseW D Knight
Dementia Research Centre, Institute of Neurology, University College London, London, UK
Eur J Neurol 14:829-31. 2007..They are, however, consistent with the reported clinical phenotype in the majority of PSEN1 exon 6 mutations so far reported... - Review: contribution of transgenic models to understanding human prion diseaseJ D F Wadsworth
MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, London, UK
Neuropathol Appl Neurobiol 36:576-97. 2010.... - Neuroimaging findings in human prion diseaseR G MacFarlane
MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, London, UK
J Neurol Neurosurg Psychiatry 78:664-70. 2007..This paper reviews the current knowledge of imaging appearances in human prion disease... - Regional brain metabolite abnormalities in inherited prion disease and asymptomatic gene carriers demonstrated in vivo by quantitative proton magnetic resonance spectroscopyA D Waldman
Dementia Research Group, Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London, WC1 3BG, UK
Neuroradiology 48:428-33. 2006.... - Elongated oligomers assemble into mammalian PrP amyloid fibrilsM Howard Tattum
MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
J Mol Biol 357:975-85. 2006.... - IntroductionJohn Collinge
Department of Neurodegenerative Disease, MRC Prion Unit, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
Philos Trans R Soc Lond B Biol Sci 363:3607-12. 2008 - Prion strains and species barriersAndrew F Hill
MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, London, UK
Contrib Microbiol 11:33-49. 2004 - The cellular prion protein is preferentially expressed by CD4+ CD25+ Foxp3+ regulatory T cellsJeremy D Isaacs
Department of Infectious Diseases and Immunity, Imperial College, Hammersmith Hospital, London, UK
Immunology 125:313-9. 2008..Nevertheless, the preferential expression of surface PrP(C) by regulatory T cells raises the possibility that therapeutic ligation of PrP(C) might alter immune regulation... - Age of onset and death in inherited prion disease are heritableT E F Webb
MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
Am J Med Genet B Neuropsychiatr Genet 150:496-501. 2009.... - Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international seriesT E F Webb
Department of Neurodegenerative Disease and MRC Prion Unit, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
Brain 131:2632-46. 2008..These data allow an appreciation of the range of clinical phenotype, modern imaging and molecular investigation and should inform genetic counselling of at-risk individuals, with the identification of two genetic modifiers... - Chromosome 14 familial Alzheimer's disease: the clinical and neuropathological characteristics of a family with a leucine-->serine (L250S) substitution at codon 250 of the presenilin 1 geneR J Harvey
Dementia Research Group, The National Hospital for Neurology and Neurosurgery and Imperial College School of Medicine at St Mary s, London, UK
J Neurol Neurosurg Psychiatry 64:44-9. 1998.... - The neuropsychology of variant CJD: a comparative study with inherited and sporadic forms of prion diseaseR J Cordery
Dementia Research Group, The National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
J Neurol Neurosurg Psychiatry 76:330-6. 2005..The results also suggest that nominal function may be preserved in some cases with inherited prion disease... - Human prion diseases and bovine spongiform encephalopathy (BSE)J Collinge
Prion Disease Group, Neurogenetics Unit, Imperial College School of Medicine at St Mary s, London, UK
Hum Mol Genet 6:1699-705. 1997..Such molecular analysis of prion strains suggests that new variant Creutzfeldt-Jakob disease is caused by BSE exposure. The novel biology of prion propagation may not be unique to these rare degenerative brain diseases... - Early onset familial Alzheimer's disease: Mutation frequency in 31 familiesJ C Janssen
Dementia Research Group, Department of Clinical Neurology, Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK
Neurology 60:235-9. 2003..There may be a further genetic factor involved in the etiology of autosomal dominant early onset AD... - A systematic review of prion therapeutics in experimental modelsClare R Trevitt
MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London, UK
Brain 129:2241-65. 2006.... - Preventing prion pathogenicity by targeting the cellular prion proteinAndrew J Nicoll
Department of Neurodegenerative Disease, MRC Prion Unit, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
Infect Disord Drug Targets 9:48-57. 2009..Recent work has provided proof of principle that compounds which bind selectively to the cellular prion protein could act as therapeutics for prion diseases... - Prion disease incubation time is not affected in mice heterozygous for a dynein mutationMajid Hafezparast
Department of Neurodegenerative Disease, Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
Biochem Biophys Res Commun 326:18-22. 2005..Our data indicate that the dynein mutation in the heterozygous state does not affect prion disease incubation time or its neuropathology in Loa mice... - Update on Creutzfeldt-Jakob diseaseGiovanna Mallucci
MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, National Hospital for Neurology and Neurosurgery, London WC1N 3BG, UK
Curr Opin Neurol 17:641-7. 2004..Prevention of the formation of such a species rather than PrP(Sc) accumulation itself is a clear target for prion therapeutics... - Prion diseasesEdward McKintosh
Department of Neurodegenerative Disease/MRC Prion Unit, Institute of Neurology, University College London, London, United Kingdom
J Neurovirol 9:183-93. 2003..This article reviews the history and epidemiology of these diseases, and then focuses on important areas of current research in human prion disorders... - Prion disease--the propagation of infectious protein topologiesG S Jackson
MRC Prion Unit, Department of Neurogenetics, Imperial College School of Medicine at St Mary s, W2 1PG, London, UK
Microbes Infect 2:1445-9. 2000..Concomitantly, advances in the analysis of the abnormal isoform, PrP(Sc), have expanded our knowledge on the molecular basis of prion strains and have done much to reinforce the protein-only hypothesis of prion replication... - Phenotypic variability in the brains of a family with a prion disease characterized by a 144-base pair insertion in the prion protein geneA King
Department of Neuropathology, Institute of Psychiatry, Kings College London, London, UK
Neuropathol Appl Neurobiol 29:98-105. 2003..They also reveal that the relationship between PrP deposition and cerebral or cerebellar damage might be complex... - The molecular pathology of CJD: old and new variantsG S Jackson
MRC Prion Unit, Department of Neurogenetics, Imperial College School of Medicine at St Mary s, Norfolk Place, Paddington, London W2 1NY, UK
Mol Pathol 54:393-9. 2001..Concomitantly, advances in the fundamental biology of prion disease have done much to reinforce the protein only hypothesis of prion replication... - Molecular analysis of prion strain variation and the aetiology of 'new variant' CJDJ Collinge
Neurogenetics Unit, Department of Biochemistry and Molecular Genetics, Imperial College School of Medicine at St Mary s, London, UK
Nature 383:685-90. 1996..Strain characteristics revealed here suggest that the prion protein may itself encode disease phenotype... - A presenilin 1 R278I mutation presenting with language impairmentA K Godbolt
Dementia Research Centre, Department of Neurodegenerative Disease, Institute of Neurology, London, UK
Neurology 63:1702-4. 2004..Screening for PSEN1 mutations may be appropriate in cases of familial dementia even where the clinical phenotype is not typical of AD... - Inherited prion disease with 5-OPRI: phenotype modification by repeat length and codon 129S Mead
MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London, UK
Neurology 69:730-8. 2007..An individual inherited prion disease offers an opportunity to study the determinants of this clinicopathologic heterogeneity among individuals with the same causal mutation... - The human prion protein residue 129 polymorphism lies within a cluster of epitopes for T cell recognitionJeremy D Isaacs
Human Disease Immunogenetics Group, Department of Infectious Diseases and Immunity, Imperial College, Hammersmith Hospital, London, UK
J Neuropathol Exp Neurol 65:1059-68. 2006.... - Autopsy-confirmed familial early-onset Alzheimer disease caused by the l153V presenilin 1 mutationJ C Janssen
Dementia Research Group, Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, England
Arch Neurol 58:953-8. 2001..CONCLUSIONS: The PSEN1 L153V mutation lies in the main mutation cluster of PSEN1 in the second transmembrane domain. It causes early-onset FAD with clinical features similar to those of other reported FAD pedigrees...