John Collinge

Summary

Affiliation: University College London
Country: UK

Publications

  1. pmc Introduction
    John 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
  2. pmc HECTD2 is associated with susceptibility to mouse and human prion disease
    Sarah E Lloyd
    MRC Prion Unit, University College London Institute of Neurology, London, United Kingdom
    PLoS Genet 5:e1000383. 2009
  3. pmc Absence of spontaneous disease and comparative prion susceptibility of transgenic mice expressing mutant human prion proteins
    Emmanuel 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
  4. pmc Central and peripheral pathology of kuru: pathological analysis of a recent case and comparison with other forms of human prion disease
    Sebastian Brandner
    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 363:3755-63. 2008
  5. pmc Genetic susceptibility, evolution and the kuru epidemic
    Simon 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
  6. pmc Chronic wasting disease prions are not transmissible to transgenic mice overexpressing human prion protein
    Malin 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
  7. pmc Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series
    T 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
  8. pmc Review. The origin of the prion agent of kuru: molecular and biological strain typing
    Jonathan 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
  9. pmc Inherited prion disease A117V is not simply a proteinopathy but produces prions transmissible to transgenic mice expressing homologous prion protein
    Emmanuel A Asante
    Medical Research Council Prion Unit and Department of Neurodegenerative Disease, University College London Institute of Neurology, Queen Square, London, United Kingdom
    PLoS Pathog 9:e1003643. 2013
  10. pmc A standardized comparison of commercially available prion decontamination reagents using the Standard Steel-Binding Assay
    Julie Ann Edgeworth
    MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK
    J Gen Virol 92:718-26. 2011

Detail Information

Publications144 found, 100 shown here

  1. pmc Introduction
    John 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
  2. pmc HECTD2 is associated with susceptibility to mouse and human prion disease
    Sarah 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...
  3. pmc Absence of spontaneous disease and comparative prion susceptibility of transgenic mice expressing mutant human prion proteins
    Emmanuel 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...
  4. pmc Central and peripheral pathology of kuru: pathological analysis of a recent case and comparison with other forms of human prion disease
    Sebastian Brandner
    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 363:3755-63. 2008
    ..These findings now strongly suggest that the characteristic peripheral pathogenesis of vCJD is determined by prion strain type alone rather than route of infection...
  5. pmc Genetic susceptibility, evolution and the kuru epidemic
    Simon 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...
  6. pmc Chronic wasting disease prions are not transmissible to transgenic mice overexpressing human prion protein
    Malin 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...
  7. pmc Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series
    T 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...
  8. pmc Review. The origin of the prion agent of kuru: molecular and biological strain typing
    Jonathan 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...
  9. pmc Inherited prion disease A117V is not simply a proteinopathy but produces prions transmissible to transgenic mice expressing homologous prion protein
    Emmanuel A Asante
    Medical Research Council Prion Unit and Department of Neurodegenerative Disease, University College London Institute of Neurology, Queen Square, London, United Kingdom
    PLoS Pathog 9:e1003643. 2013
    ..We conclude that GSS A117V is indeed a prion disease although the relative contributions of (Ctm)PrP and prion propagation in neurodegeneration and their pathogenetic interaction remains to be established...
  10. pmc A standardized comparison of commercially available prion decontamination reagents using the Standard Steel-Binding Assay
    Julie Ann Edgeworth
    MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK
    J Gen Virol 92:718-26. 2011
    ..We demonstrate that the efficacy of marketed prion decontamination reagents is highly variable and that the SSBA is able to rapidly evaluate current and future decontamination reagents...
  11. pmc Genetics of prion diseases
    Sarah E Lloyd
    MRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG, UK
    Curr Opin Genet Dev 23:345-51. 2013
    ..Expression profiling has identified new candidates, including Hspa13, which reduces incubation time in a transgenic model. ..
  12. doi request reprint The Medical Research Council prion disease rating scale: a new outcome measure for prion disease therapeutic trials developed and validated using systematic observational studies
    Andrew 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...
  13. pmc Molecular pathology of human prion disease
    Jonathan 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...
  14. pmc Review. Lessons of kuru research: background to recent studies with some personal reflections
    John 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...
  15. pmc Reminiscences and reflections on kuru, personal and scientific
    John 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
  16. pmc A clinical study of kuru patients with long incubation periods at the end of the epidemic in Papua New Guinea
    John 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...
  17. pmc Molecular neurology of prion disease
    J 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
    ....
  18. pmc Safety and efficacy of quinacrine in human prion disease (PRION-1 study): a patient-preference trial
    John 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
    ....
  19. ncbi request reprint A general model of prion strains and their pathogenicity
    John 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...
  20. ncbi request reprint Kuru in the 21st century--an acquired human prion disease with very long incubation periods
    John 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...
  21. ncbi request reprint Human prion protein with valine 129 prevents expression of variant CJD phenotype
    Jonathan 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...
  22. pmc Genetic risk factors for variant Creutzfeldt-Jakob disease: a genome-wide association study
    Simon Mead
    Medical Research Council Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London, UK
    Lancet Neurol 8:57-66. 2009
    ....
  23. doi request reprint The H187R mutation of the human prion protein induces conversion of recombinant prion protein to the PrP(Sc)-like form
    Laszlo 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...
  24. doi request reprint A novel protective prion protein variant that colocalizes with kuru exposure
    Simon Mead
    Medical Research Council Prion Unit, Department of Neurodegenerative Disease, University College London Institute of Neurology, United Kingdom
    N Engl J Med 361:2056-65. 2009
    ..Its incidence has steadily declined since the cessation of its route of transmission, endocannibalism...
  25. ncbi request reprint Balancing selection at the prion protein gene consistent with prehistoric kurulike epidemics
    Simon 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...
  26. ncbi request reprint Distinct glycoform ratios of protease resistant prion protein associated with PRNP point mutations
    Andrew 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...
  27. pmc Conformational properties of beta-PrP
    Laszlo 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...
  28. ncbi request reprint Inherited prion disease with six octapeptide repeat insertional mutation--molecular analysis of phenotypic heterogeneity
    Simon Mead
    MRC Prion Unit, Department of Neurodegenerative Diseases, Institute of Neurology, King s College Hospital, London, UK
    Brain 129:2297-317. 2006
    ....
  29. pmc Kuru prions and sporadic Creutzfeldt-Jakob disease prions have equivalent transmission properties in transgenic and wild-type mice
    Jonathan 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...
  30. pmc Large C9orf72 hexanucleotide repeat expansions are seen in multiple neurodegenerative syndromes and are more frequent than expected in the UK population
    Jon Beck
    Medical Research Council Prion Unit, Department of Neurodegenerative Disease, University College London Institute of Neurology, Queen Square, London, UK
    Am J Hum Genet 92:345-53. 2013
    ..C9orf72-related disease might mimic several neurodegenerative disorders and, with potentially 90,000 carriers in the United Kingdom, is more common than previously realized...
  31. ncbi request reprint Beta-PrP form of human prion protein stimulates production of monoclonal antibodies to epitope 91-110 that recognise native PrPSc
    Azadeh 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)...
  32. ncbi request reprint Molecular and clinical classification of human prion disease
    Jonathan 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...
  33. ncbi request reprint Phenotypic heterogeneity in inherited prion disease (P102L) is associated with differential propagation of protease-resistant wild-type and mutant prion protein
    Jonathan 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...
  34. ncbi request reprint PrP glycoforms are associated in a strain-specific ratio in native PrPSc
    Azadeh 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...
  35. ncbi request reprint Identification and characterization of a novel mouse prion gene allele
    Sarah 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...
  36. pmc Homozygosity for the C9orf72 GGGGCC repeat expansion in frontotemporal dementia
    Pietro Fratta
    Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK
    Acta Neuropathol 126:401-9. 2013
    ..Our findings have implications for genetic counselling, highlighting the need to use genetic tests that distinguish C9orf72 homozygosity. ..
  37. ncbi request reprint Codon 129 polymorphism of the human prion protein influences the kinetics of amyloid formation
    Patrick 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...
  38. ncbi request reprint Disease-associated prion protein oligomers inhibit the 26S proteasome
    Mark 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...
  39. pmc A distinct clinical, neuropsychological and radiological phenotype is associated with progranulin gene mutations in a large UK series
    Jonathan 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...
  40. pmc Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP
    Simon 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...
  41. doi request reprint Progressive neuronal inclusion formation and axonal degeneration in CHMP2B mutant transgenic mice
    Shabnam 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...
  42. doi request reprint PRNP allelic series from 19 years of prion protein gene sequencing at the MRC Prion Unit
    Jon 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...
  43. pmc Mapping the progression of progranulin-associated frontotemporal lobar degeneration
    Jonathan 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...
  44. pmc Parietal lobe deficits in frontotemporal lobar degeneration caused by a mutation in the progranulin gene
    Jonathan 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)...
  45. doi request reprint Inherited prion disease with 4-octapeptide repeat insertion: disease requires the interaction of multiple genetic risk factors
    Diego 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...
  46. pmc Dissociation of pathological and molecular phenotype of variant Creutzfeldt-Jakob disease in transgenic human prion protein 129 heterozygous mice
    Emmanuel 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...
  47. pmc Single treatment with RNAi against prion protein rescues early neuronal dysfunction and prolongs survival in mice with prion disease
    Melanie 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
    ....
  48. ncbi request reprint Analysis of 2000 consecutive UK tonsillectomy specimens for disease-related prion protein
    Adam 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...
  49. pmc Overexpression of the Hspa13 (Stch) gene reduces prion disease incubation time in mice
    Julia Grizenkova
    Medical Research Council MRC Prion Unit, University College London UCL Institute of Neurology, London, United Kingdom
    Proc Natl Acad Sci U S A 109:13722-7. 2012
    ..These data further implicate Hsp70-like molecular chaperones in protein misfolding disorders such as prion disease...
  50. ncbi request reprint The residue 129 polymorphism in human prion protein does not confer susceptibility to Creutzfeldt-Jakob disease by altering the structure or global stability of PrPC
    Laszlo 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...
  51. pmc A Copine family member, Cpne8, is a candidate quantitative trait gene for prion disease incubation time in mouse
    Sarah 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...
  52. pmc BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein
    Emmanuel 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...
  53. ncbi request reprint Disease-related prion protein forms aggresomes in neuronal cells leading to caspase activation and apoptosis
    Mark 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...
  54. ncbi request reprint Creutzfeldt-Jakob disease, prion protein gene codon 129VV, and a novel PrPSc type in a young British woman
    Simon 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...
  55. ncbi request reprint Definable equilibrium states in the folding of human prion protein
    Laszlo 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...
  56. pmc Investigation of mcp1 as a quantitative trait gene for prion disease incubation time in mouse
    Marie 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...
  57. pmc Tau, prions and Aβ: the triad of neurodegeneration
    Lilla 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...
  58. ncbi request reprint An enzyme-detergent method for effective prion decontamination of surgical steel
    Graham 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...
  59. pmc Pharmacological chaperone for the structured domain of human prion protein
    Andrew J Nicoll
    Department of Neurodegenerative Disease and Medical Research Council Prion Unit, University College of London Institute of Neurology, Queen Square, London WCN1 3BG, United Kingdom
    Proc Natl Acad Sci U S A 107:17610-5. 2010
    ..The identification of a binding site with a defined 3D structure opens up the possibility of designing small molecules that stabilize huPrP and prevent its conversion into the disease-associated form...
  60. ncbi request reprint First report of Creutzfeldt-Jakob disease occurring in 2 siblings unexplained by PRNP mutation
    Thomas E F Webb
    National Prion Clinic, National Hospital for Neurology and Neurosurgery, UCLH Hospitals Trust, Queen Square, London, United Kingdom
    J Neuropathol Exp Neurol 67:838-41. 2008
    ..Possible explanations include coincidental occurrence, common exposure to an unidentified environmental source of prions, horizontal transmission of disease, or the presence of unknown shared genetic predisposition...
  61. doi request reprint Detection of prion infection in variant Creutzfeldt-Jakob disease: a blood-based assay
    Julie 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...
  62. pmc Spontaneous generation of mammalian prions
    Julie 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...
  63. ncbi request reprint Subclinical prion infection in humans and animals
    Andrew 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...
  64. doi request reprint Prion propagation and toxicity in vivo occur in two distinct mechanistic phases
    Malin 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...
  65. doi request reprint Molecular diagnosis of human prion disease
    Jonathan D F Wadsworth
    MRC Prion Unit, University College London Institute of Neurology, London, UK
    Methods Mol Biol 459:197-227. 2008
    ....
  66. pmc Isolation of proteinase K-sensitive prions using pronase E and phosphotungstic acid
    Laura 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)...
  67. pmc Superoxide dismutase 1 and tgSOD1 mouse spinal cord seed fibrils, suggesting a propagative cell death mechanism in amyotrophic lateral sclerosis
    Ruth 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...
  68. pmc Detection and characterization of proteinase K-sensitive disease-related prion protein with thermolysin
    Sabrina 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...
  69. doi request reprint Effect of fixation on brain and lymphoreticular vCJD prions and bioassay of key positive specimens from a retrospective vCJD prevalence study
    Jonathan 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...
  70. ncbi request reprint Targeting cellular prion protein reverses early cognitive deficits and neurophysiological dysfunction in prion-infected mice
    Giovanna 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...
  71. pmc Recombinant prion protein does not possess SOD-1 activity
    Samantha 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...
  72. ncbi request reprint Characterization of two distinct prion strains derived from bovine spongiform encephalopathy transmissions to inbred mice
    Sarah 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...
  73. pmc HECTD2, a candidate susceptibility gene for Alzheimer's disease on 10q
    Sarah 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...
  74. doi request reprint Magnetization transfer ratio may be a surrogate of spongiform change in human prion diseases
    Durrenajaf 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...
  75. pmc Removal of the glycosylphosphatidylinositol anchor from PrP(Sc) by cathepsin D does not reduce prion infectivity
    Patrick 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...
  76. ncbi request reprint Protein conformation significantly influences immune responses to prion protein
    Azadeh 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...
  77. ncbi request reprint Inhibition of proteinase K activity by copper(II) ions
    Lisa 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...
  78. ncbi request reprint Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt-Jakob disease associated with blood transfusion: a case report
    Stephen J Wroe
    National Prion Clinic, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
    Lancet 368:2061-7. 2006
    ..Another patient from this at-risk group developed neurological signs and was referred to the National Prion Clinic...
  79. pmc Folding kinetics of the human prion protein probed by temperature jump
    Tanya 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...
  80. ncbi request reprint Pathogenic human prion protein rescues PrP null phenotype in transgenic mice
    Emmanuel 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...
  81. ncbi request reprint Identification of genetic loci affecting mouse-adapted bovine spongiform encephalopathy incubation time in mice
    Sarah 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...
  82. ncbi request reprint Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis
    Giovanna 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...
  83. ncbi request reprint Species-barrier-independent prion replication in apparently resistant species
    Andrew 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...
  84. pmc Shadoo (Sprn) and prion disease incubation time in mice
    Sarah 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...
  85. pmc Mortuary rites of the South Fore and kuru
    Jerome 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...
  86. doi request reprint A novel exon 2 I27V VCP variant is associated with dissimilar clinical syndromes
    Jonathan 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...
  87. pmc Neuroimaging findings in human prion disease
    R 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...
  88. ncbi request reprint Regional brain metabolite abnormalities in inherited prion disease and asymptomatic gene carriers demonstrated in vivo by quantitative proton magnetic resonance spectroscopy
    A 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
    ....
  89. ncbi request reprint A novel presenilin 1 deletion (p.L166del) associated with early onset familial Alzheimer's disease
    W 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...
  90. pmc Review: contribution of transgenic models to understanding human prion disease
    J 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
    ....
  91. ncbi request reprint Elongated oligomers assemble into mammalian PrP amyloid fibrils
    M 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
    ....
  92. ncbi request reprint Prion strains and species barriers
    Andrew F Hill
    MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, London, UK
    Contrib Microbiol 11:33-49. 2004
  93. pmc The cellular prion protein is preferentially expressed by CD4+ CD25+ Foxp3+ regulatory T cells
    Jeremy 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...
  94. doi request reprint Age of onset and death in inherited prion disease are heritable
    T 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
    ....
  95. ncbi request reprint Early onset familial Alzheimer's disease: Mutation frequency in 31 families
    J 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
    ..Three causative genes have been identified for autosomal dominant AD...
  96. pmc 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 gene
    R 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
    ....
  97. pmc The neuropsychology of variant CJD: a comparative study with inherited and sporadic forms of prion disease
    R 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
    ....
  98. ncbi request reprint 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...
  99. ncbi request reprint A systematic review of prion therapeutics in experimental models
    Clare 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
    ....
  100. ncbi request reprint Prion diseases
    Edward 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...
  101. ncbi request reprint Preventing prion pathogenicity by targeting the cellular prion protein
    Andrew 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...