D R Brown

Summary

Affiliation: University of Bath
Country: UK

Publications

  1. ncbi request reprint Prion protein reduces both oxidative and non-oxidative copper toxicity
    Cathryn L Haigh
    Department of Biology and Biochemistry, University of Bath, Bath, UK
    J Neurochem 98:677-89. 2006
  2. doi request reprint Manganese binding to the prion protein
    Marcus W Brazier
    Department of Biology and Biochemistry and Chemistry, University of Bath, Bath BA2 7AY, UK
    J Biol Chem 283:12831-9. 2008
  3. ncbi request reprint Inhibition of tumour necrosis factor-alpha (TNFalpha)-induced NF-kappaB p52 converts the metabolic effects of microglial-derived TNFalpha on mouse cerebellar neurones to neurotoxicity
    R S Nicholas
    University of Cambridge Neurology Unit, Addenbrooke's Hospital, Hills Road, Cambridge, UK
    J Neurochem 76:1431-8. 2001
  4. doi request reprint Alpha-synuclein: relating metals to structure, function and inhibition
    J S McDowall
    Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK
    Metallomics 8:385-97. 2016
  5. doi request reprint Brain proteins that mind metals: a neurodegenerative perspective
    David R Brown
    Department of Biology, University of Bath, Bath, UKBA2 7AY
    Dalton Trans . 2009
  6. ncbi request reprint Biological inorganic and bioinorganic chemistry of neurodegeneration based on prion and Alzheimer diseases
    David R Brown
    Department of Biology and Biochemistry, University of Bath, UK BA2 7AY
    Dalton Trans . 2004
  7. ncbi request reprint Metallic prions
    David R Brown
    Department of Biology and Biochemistry, 4 South, University of Bath, Calverton Down, Bath BA2 7AY, U K
    Biochem Soc Symp . 2004
  8. pmc Manganese enhances prion protein survival in model soils and increases prion infectivity to cells
    Paul Davies
    Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom
    PLoS ONE 4:e7518. 2009
  9. pmc Transcriptional regulation of the beta-synuclein 5'-promoter metal response element by metal transcription factor-1
    Patrick C McHugh
    Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, United Kingdom
    PLoS ONE 6:e17354. 2011
  10. pmc Alpha-synuclein is a cellular ferrireductase
    Paul Davies
    Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom
    PLoS ONE 6:e15814. 2011

Collaborators

Detail Information

Publications93

  1. ncbi request reprint Prion protein reduces both oxidative and non-oxidative copper toxicity
    Cathryn L Haigh
    Department of Biology and Biochemistry, University of Bath, Bath, UK
    J Neurochem 98:677-89. 2006
    ..Our findings demonstrate that copper toxicity can be independent of measured oxidative stress and that prion protein expression primarily protects against copper toxicity independently of the mechanism of cell death...
  2. doi request reprint Manganese binding to the prion protein
    Marcus W Brazier
    Department of Biology and Biochemistry and Chemistry, University of Bath, Bath BA2 7AY, UK
    J Biol Chem 283:12831-9. 2008
    ..These results further support the notion that manganese binding could cause a conformation change in PrP and trigger changes in the protein similar to those associated with prion disease...
  3. ncbi request reprint Inhibition of tumour necrosis factor-alpha (TNFalpha)-induced NF-kappaB p52 converts the metabolic effects of microglial-derived TNFalpha on mouse cerebellar neurones to neurotoxicity
    R S Nicholas
    University of Cambridge Neurology Unit, Addenbrooke's Hospital, Hills Road, Cambridge, UK
    J Neurochem 76:1431-8. 2001
    ..Characterizing and manipulating these events in vivo theoretically provides an opportunity for neuroprotection in selected diseases affecting the central nervous system...
  4. doi request reprint Alpha-synuclein: relating metals to structure, function and inhibition
    J S McDowall
    Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK
    Metallomics 8:385-97. 2016
    ..The recent proposal that alpha-synuclein is a ferrireductase is important as it can possibly catalyse the formation of such reactive species and as a result exacerbate neurodegeneration. ..
  5. doi request reprint Brain proteins that mind metals: a neurodegenerative perspective
    David R Brown
    Department of Biology, University of Bath, Bath, UKBA2 7AY
    Dalton Trans . 2009
    ..Therefore, recent insights into the metallochemistry of the prion protein are relevant to investigating APP and alpha-synuclein. This review considers what is known of the metallochemistry of all three proteins...
  6. ncbi request reprint Biological inorganic and bioinorganic chemistry of neurodegeneration based on prion and Alzheimer diseases
    David R Brown
    Department of Biology and Biochemistry, University of Bath, UK BA2 7AY
    Dalton Trans . 2004
    ..Also APP is a metal binding protein, including copper ions. The link between copper and both proteins may provide insight into the role of metals in neurodegenerative pathologies...
  7. ncbi request reprint Metallic prions
    David R Brown
    Department of Biology and Biochemistry, 4 South, University of Bath, Calverton Down, Bath BA2 7AY, U K
    Biochem Soc Symp . 2004
    ..Thus prions and metals have become tightly linked in the quest to understand the nature of transmissible spongiform encephalopathies...
  8. pmc Manganese enhances prion protein survival in model soils and increases prion infectivity to cells
    Paul Davies
    Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom
    PLoS ONE 4:e7518. 2009
    ..These results clearly verify that manganese is a risk factor for both the survival of the infectious agent in the environment and its transmissibility...
  9. pmc Transcriptional regulation of the beta-synuclein 5'-promoter metal response element by metal transcription factor-1
    Patrick C McHugh
    Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, United Kingdom
    PLoS ONE 6:e17354. 2011
    ..This could potentially provide a novel targets or pathways for therapeutic intervention and/or treatment of synucleinopathies...
  10. pmc Alpha-synuclein is a cellular ferrireductase
    Paul Davies
    Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom
    PLoS ONE 6:e15814. 2011
    ..The common disease mutations associated with increased susceptibility to PD show no [corrected] differences in activity or iron (II) levels. This discovery may well provide new therapeutic targets for PD and Lewy body dementias...
  11. doi request reprint Modelling neurodegeneration in prion disease - applications for drug development
    Kay M Uppington
    University of Bath, Department of Biology and Biochemistry, Bath, Claverton Down, BA2 7AY, UK 44 1255 383133 44 1225 386779
    Expert Opin Drug Discov 2:777-88. 2007
    ..So far, there are no effective therapies available for prion diseases. This review discusses possible therapies for prion diseases and the models available for advancing research into the disease...
  12. doi request reprint Gene regulation as a potential avenue for the treatment of neurodegenerative disorders
    David R Brown
    University of Bath, Department of Biology and Biochemistry, Bath, BA2 7AY, UK 44 1225 383133 44 1225 386779
    Expert Opin Drug Discov 4:515-24. 2009
    ..Clearly, the prevention of this process is a key therapeutic target...
  13. ncbi request reprint Prion protein expression modulates neuronal copper content
    David R Brown
    Department of Biology and Biochemistry, University of Bath, Cambridge, UK
    J Neurochem 87:377-85. 2003
    ..Loss of normal Cu binding by the prion protein altered age-related increases in metals in the brain. This may explain why many forms of human prion disease do not develop until late in life...
  14. ncbi request reprint Role of the prion protein in copper turnover in astrocytes
    David R Brown
    Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, United Kingdom
    Neurobiol Dis 15:534-43. 2004
    ..These results indicate that PrP(c) plays a role in the regulation of Cu taken up by astrocytes and potentially protects neurones from Cu toxicity by this mechanism...
  15. ncbi request reprint Conformational exposure: a new handle on prions
    David R Brown
    Department of Biology and Biochemistry, University of Bath, BA2 7AY, Bath, UK
    Lancet 362:929-30. 2003
  16. ncbi request reprint Neurodegeneration and oxidative stress: prion disease results from loss of antioxidant defence
    David R Brown
    Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, UK
    Folia Neuropathol 43:229-43. 2005
    ..This failed defence is the fundamental cause of the massive neurodegeneration that results in the fatal nature of TSEs. The role of oxidative stress in TSEs and other neurodegenerative disorders are discussed in this review...
  17. ncbi request reprint Interactions between metals and alpha-synuclein--function or artefact?
    David R Brown
    Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, UK
    FEBS J 274:3766-74. 2007
    ..This review examines the evidence that alpha-synuclein is a copper binding protein and discusses whether this has any significance in determining the function of the protein or whether copper binding is at all necessary for aggregation...
  18. doi request reprint Metal binding to alpha-synuclein peptides and its contribution to toxicity
    David R Brown
    Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK
    Biochem Biophys Res Commun 380:377-81. 2009
    ..We hypothesise that copper binding can cause conversion of AS to a neurotoxic form via inter-protein interactions...
  19. ncbi request reprint Copper-dependent functions for the prion protein
    David R Brown
    Department of Biology and Biochemistry, University of Bath, UK
    Mol Biotechnol 22:165-78. 2002
    ..Conversion of the prion protein to an abnormal isoform might lead to a loss of antioxidant protection that could be responsible for neurodegeneration in the disease...
  20. doi request reprint Role of microglia in age-related changes to the nervous system
    David R Brown
    Department of Biology and Biochemistry, University of Bath, UK
    ScientificWorldJournal 9:1061-71. 2009
    ..This review provides illustrations of what is known about the role of microglia in neurodegeneration and makes suggestions about the role of microglia in age-related changes to the brain...
  21. ncbi request reprint Copper and prion diseases
    D R Brown
    Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
    Biochem Soc Trans 30:742-5. 2002
    ..There is growing evidence that links prion diseases to disturbances of metal metabolism...
  22. ncbi request reprint Mayhem of the multiple mechanisms: modelling neurodegeneration in prion disease
    David R Brown
    Department of Biology and Biochemistry, University of Bath, Bath, UK
    J Neurochem 82:209-15. 2002
    ..Thus understanding the mechanism by which the abnormal form of the prion protein causes neuronal death might lead to treatments that would prevent the life-threatening nature of these diseases...
  23. ncbi request reprint Molecular advances in understanding inherited prion diseases
    David R Brown
    Department of Biology and Biochemistry, Bath University, UK
    Mol Neurobiol 25:287-302. 2002
    ..This review deals with the latest insights into how inherited mutations in the prion protein gene lead to neurodegenerative disease...
  24. doi request reprint Oligomeric alpha-synuclein and its role in neuronal death
    David R Brown
    Department of Biology and Biochemistry, University of Bath, Bath, UK
    IUBMB Life 62:334-9. 2010
    ..Recent research has suggested that a unique oligomer associated with the copper binding capacity of the protein is the neurotoxic form of the protein. This review looks at the evidence for this possibility...
  25. doi request reprint Metalloproteins and neuronal death
    David R Brown
    Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom BA2 7AY
    Metallomics 2:186-94. 2010
    ..This review considers the evidence that cell death in these diseases involves not just the aggregated proteins but also the metals they bind...
  26. doi request reprint Prions and manganese: A maddening beast
    David R Brown
    Department of Biology and Biochemistry, University of Bath, Bath, UKBA2 7AY
    Metallomics 3:229-38. 2011
    ..This article reviews the evidence for a link between prions and manganese...
  27. ncbi request reprint BSE did not cause variant CJD: an alternative cause related to post-industrial environmental contamination
    D R Brown
    Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
    Med Hypotheses 57:555-60. 2001
    ..Therefore it is quite possible that BSE and variant CJD have emerged as a result of manganese-rich industrial pollution that has only occurred in the last century...
  28. ncbi request reprint Copper and prion disease
    D R Brown
    Department of Biochemistry, Cambridge University, Cambridge, UK
    Brain Res Bull 55:165-73. 2001
    ..This conversion may alter the function of the prion protein or abolish it. These results suggest that prion disease may involve disturbance to brain copper homeostasis...
  29. doi request reprint The effects of prion protein expression on metal metabolism
    Silvia Kralovicova
    Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA27AY, UK
    Mol Cell Neurosci 41:135-47. 2009
    ..The implication is that prion protein expression has a homeostatic role in copper metabolism...
  30. ncbi request reprint Antioxidant activity related to copper binding of native prion protein
    D R Brown
    Department of Biochemistry, Cambridge University, Cambridge, UK
    J Neurochem 76:69-76. 2001
    ..These results suggest that PrP(c) is a copper-binding protein which can incorporate varying amounts of copper and exhibit protective antioxidant activity...
  31. ncbi request reprint High affinity binding between copper and full-length prion protein identified by two different techniques
    Andrew R Thompsett
    Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, United Kingdom
    J Biol Chem 280:42750-8. 2005
    ..The copper binding affinities of PrP have been compared with those of proteins of known function and are of magnitudes compatible with an extracellular copper buffer or an enzymatic function such as superoxide dismutase like activity...
  32. ncbi request reprint BSE and vCJD cause disturbance to uric acid levels
    Tamuna Lekishvili
    Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK
    Exp Neurol 190:233-44. 2004
    ..These findings suggest that changes in uric acid may aid differential diagnosis of vCJD. Uric acid could be used to inhibit cell death or PrP(Sc) formation in prion disease...
  33. ncbi request reprint Prion protein expression aids cellular uptake and veratridine-induced release of copper
    D R Brown
    Department of Biochemistry and MRC Cambridge Centre for Brain Repair, Cambridge University, Cambridge, United Kingdom
    J Neurosci Res 58:717-25. 1999
    ..These results suggest that PrP(c) aids cellular copper uptake and may have a function at the synapse related to release of copper during transmission...
  34. ncbi request reprint Dual polarisation interferometry analysis of copper binding to the prion protein: evidence for two folding states
    Andrew R Thompsett
    Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK
    Biochim Biophys Acta 1774:920-7. 2007
    ..This technique could be important not only for the study of metal-protein interactions but also small structural differences that could define prion strains...
  35. ncbi request reprint Analysis of doppel protein toxicity
    Taian Cui
    Department of Biology and Biochemistry, Bath University, UK
    Mol Cell Neurosci 23:144-55. 2003
    ..This mechanism of toxicity is quite different from that of PrP(Sc) and does not require the protein to change conformation. These results provide the first evidence for the mechanism of Dpl toxicity...
  36. ncbi request reprint Astrocytic regulation of NMDA receptor subunit composition modulates the toxicity of prion peptide PrP106-126
    Judyth Sassoon
    Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
    Mol Cell Neurosci 25:181-91. 2004
    ..The results of these experiments suggest neuronal death in prion disease might be reduced by the use of NMDA receptor antagonists such as MK801 or inhibitors of the arachidonic acid metabolism pathway...
  37. ncbi request reprint Elevated manganese levels in blood and central nervous system occur before onset of clinical signs in scrapie and bovine spongiform encephalopathy
    S Hesketh
    Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, UK
    J Anim Sci 85:1596-609. 2007
    ..These findings suggest that elevated blood Mn could be a potential diagnostic marker for prion infection even in the absence of apparent clinical disease...
  38. ncbi request reprint Copper(II) complexes of peptide fragments of the prion protein. Conformation changes induced by copper(II) and the binding motif in C-terminal protein region
    David R Brown
    Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
    J Inorg Biochem 98:133-43. 2004
    ..The similarity of the EPR parameters suggests that the anchoring imidazole residue drives the copper(II) coordination environment towards a common binding motif in different regions of the prion protein...
  39. ncbi request reprint A novel method of generating neuronal cell lines from gene-knockout mice to study prion protein membrane orientation
    Andrea Holme
    Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK
    Eur J Neurosci 18:571-9. 2003
    ..Our results suggest that these mutations do not create transmembrane forms of the protein, but block normal transport of PrP to the cell membrane...
  40. doi request reprint The chemistry of copper binding to PrP: is there sufficient evidence to elucidate a role for copper in protein function?
    Paul Davies
    Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, U K
    Biochem J 410:237-44. 2008
    ..No clear conclusions can be made from the available data, but it is clear from the present review what aspects of copper association with PrP need to be re-investigated...
  41. doi request reprint Copper binding regulates intracellular alpha-synuclein localisation, aggregation and toxicity
    Xiaoyan Wang
    Department of Biology and Biochemistry, University of Bath, Bath, UK
    J Neurochem 113:704-14. 2010
    ..These results suggest that the potential pathological role of alpha-synuclein aggregates is dependent upon the copper binding capacity of the protein...
  42. ncbi request reprint Microglia and prion disease
    D R Brown
    Department of Biochemistry, Cambridge University, Cambridge, CB2 1QW, United Kingdom
    Microsc Res Tech 54:71-80. 2001
    ..The implication of this is that microglia may play a major role in initiating the pathological changes in prion disease. This review discusses the role of microglia in these changes...
  43. ncbi request reprint Hydrogen peroxide cleavage of the prion protein generates a fragment able to initiate polymerisation of full length prion protein
    Salama R Abdelraheim
    Department of Biology and Biochemistry, University of Bath, Calverton Down, Bath BA2 7AY, United Kingdom
    Int J Biochem Cell Biol 38:1429-40. 2006
    ..Therefore our results provide a possible mechanism by which altered cleavage of the prion protein could result in the kind of protein polymerisation associated with prion diseases...
  44. doi request reprint Thermodynamic and voltammetric characterization of the metal binding to the prion protein: insights into pH dependence and redox chemistry
    Paul Davies
    Department of Biology and Biochemistry, University of Bath, Bath, UK
    Biochemistry 48:2610-9. 2009
    ..These results show conclusively that PrP can utilize copper for electron transfer, which would be expected for a radical detoxifying enzyme, and that the octarepeat region is the functional domain...
  45. ncbi request reprint Lack of prion protein expression results in a neuronal phenotype sensitive to stress
    David R Brown
    Department of Biochemistry, Cambridge University, Cambridge, United Kingdom
    J Neurosci Res 67:211-24. 2002
    ..The implication of these results is that the consequence of genetic ablation of genes must include biochemical analysis as well as analyses of possible developmental and behavioral changes...
  46. ncbi request reprint Copper binding is the governing determinant of prion protein turnover
    Cathryn L Haigh
    Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK
    Mol Cell Neurosci 30:186-96. 2005
    ..These results have implications for both normal metabolism of PrP(c) and the possible mechanism of conversion of PrP(c) to PrP(sc)...
  47. ncbi request reprint Mapping the functional domain of the prion protein
    Taian Cui
    Department of Biology and Biochemistry, University of Bath, UK
    Eur J Biochem 270:3368-76. 2003
    ..These regions show high evolutionary conservation fitting with the idea that they are important to the active domain of the protein...
  48. ncbi request reprint Regulation of prion protein expression by noncoding regions of the Prnp gene
    Cathryn L Haigh
    Department of Biology and Biochemistry, University of Bath, Bath, UK
    J Mol Biol 368:915-27. 2007
    ..Because switching off prion protein expression has been shown to arrest prion disease, these regions present novel targets for intervention in the disease process...
  49. ncbi request reprint Resistance of cell lines to prion toxicity aided by phospho-ERK expression
    Kay M Uppington
    Department of Biology and Biochemistry, University of Bath, Bath, UK
    J Neurochem 105:842-52. 2008
    ....
  50. ncbi request reprint Mouse galectin-1 inhibits the toxicity of glutamate by modifying NR1 NMDA receptor expression
    Tamuna Lekishvili
    Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, UK
    Eur J Neurosci 24:3017-25. 2006
    ..These results suggest that the astrocytic lectin galectin-1 could protect neurons against the effects of excitotoxicity as seen in stroke and ischemic injury...
  51. ncbi request reprint Mechanisms of prion protein aggregation
    Sarah N Fontaine
    Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK
    Protein Pept Lett 16:14-26. 2009
    ..This review will examine what is known about the mechanisms behind prion protein aggregation, and the relevance of each form for the disease...
  52. doi request reprint Unique copper-induced oligomers mediate alpha-synuclein toxicity
    Josephine A Wright
    Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK
    FASEB J 23:2384-93. 2009
    ..Our data provide a link between the recently noted association of copper and alpha-synuclein and a potential role for the combination in causing neurodegeneration...
  53. ncbi request reprint High extracellular potassium protects against the toxicity of cytosine arabinoside but is not required for the survival of cerebellar granule cells in vitro
    Maki Daniels
    Department of Biochemistry, Cambridge University, Cambridge, United Kingdom
    Mol Cell Neurosci 19:281-91. 2002
    ..The previously proposed role for high potassium in the survival cerebellar granule cells is rather a protective effect against toxic substances in serum such as glutamate or against agents such as Ara C...
  54. ncbi request reprint Purification and preparation of prion protein: synaptic superoxide dismutase
    Maki Daniels
    Department of Biochemistry, University of Cambridge, Cambridge, CB2 1QW, United Kingdom
    Methods Enzymol 349:258-67. 2002
  55. doi request reprint Elevated manganese levels in blood and CNS in human prion disease
    Shirley Hesketh
    Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, UK
    Mol Cell Neurosci 37:590-8. 2008
    ..However, CJD could be easily distinguished from these diseases. This implies that increased blood manganese in prion disease is a highly specific characteristic of the disease...
  56. ncbi request reprint Alpha-synuclein and its role in metal binding: relevance to Parkinson's disease
    Josephine A Wright
    Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom
    J Neurosci Res 86:496-503. 2008
    ..It was recently suggested that it binds copper. This review assesses what is known about alpha-synuclein and its interaction with metals...
  57. doi request reprint Activation and repression of prion protein expression by key regions of intron 1
    Josephine A Wright
    Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
    Cell Mol Life Sci 66:3809-20. 2009
    ..Additionally, we have identified Atox-1 as a transcription factor that upregulates prion protein expression. These findings clearly indicate that intron 1 plays a key role in regulation of prion protein expression levels...
  58. pmc Mechanistic insights into the cure of prion disease by novel antiprion compounds
    Sarah Webb
    Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom
    J Virol 81:10729-41. 2007
    ..Therefore, the principal mechanism of action of the Congo red analogues was to prevent inhibition of proteasomal activity by PrPSc...
  59. ncbi request reprint Therapeutics and prion disease: can immunisation or drugs be effective?
    J Sassoon
    Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
    Mini Rev Med Chem 5:361-6. 2005
    ..This review examines research on possible therapeutic strategies that might have potential benefits if applied before neurodegeneration has occurred...
  60. doi request reprint Amyloidogenic metal-binding proteins: new investigative pathways
    Paul Davies
    Department of Biology and Biochemistry, University of Bath, Bath, UK
    Biochem Soc Trans 36:1299-303. 2008
    ..The similarities between these proteins, in terms of metal binding, has allowed us to investigate them using similar approaches. In the present review, we discuss some of these approaches...
  61. ncbi request reprint Copper and amyloid fibril formation
    David R Brown
    Department of Biology and Biochemistry, University of Bath, UK
    FEBS J 274:3755. 2007
  62. ncbi request reprint Ancient conserved domain protein-1 binds copper and modifies its retention in cells
    Alexandra Alderton
    Department of Biology and Biochemistry, University of Bath, Bath, UK
    J Neurochem 103:312-21. 2007
    ..As our findings place the subcellular localisation of ACDP-1 in the cytoplasm it is possible that ACDP-1 represent a novel copper chaperone or storage protein...
  63. ncbi request reprint Quinacrine acts as an antioxidant and reduces the toxicity of the prion peptide PrP106-126
    Stuart Turnbull
    Department of Biological Sciences, Lancaster University, Lancaster LA1 4YQ, UK
    Neuroreport 14:1743-5. 2003
    ..Furthermore, the toxicity of PrP106-126 to cultured cells was significantly inhibited by quinacrine...
  64. ncbi request reprint Preferential Cu2+ coordination by His96 and His111 induces beta-sheet formation in the unstructured amyloidogenic region of the prion protein
    Christopher E Jones
    School of Biological Sciences, Queen Mary, University of London, United Kingdom
    J Biol Chem 279:32018-27. 2004
    ..The role of Cu(2+) in prion misfolding and disease must now be re-evaluated in the light of these findings...
  65. ncbi request reprint Synthesis of analogues of Congo red and evaluation of their anti-prion activity
    Shane Sellarajah
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK
    J Med Chem 47:5515-34. 2004
    ..A number of analogues showed inhibition of PrP-res infectivity at nanomolar concentrations. Several analogues show promise; the most active compound, 2a, inhibits the formation of PrP-res in SMB cells with an EC50 of 25-50 nM...
  66. ncbi request reprint Prion protein fate governed by metal binding
    Roumiana N Tsenkova
    Department of Bioproduction Engineering, Faculty of Engineering, Kobe University, 1 1 Rokkodai, Nada, Kobe 657 8501, Japan
    Biochem Biophys Res Commun 325:1005-12. 2004
    ..PrP-Mn does not protect Mn from water interactions. A real-time study of the protein alloforms showed that PrP-Cu remains stable in solution, but that PrP-Mn underwent highly different changes that led to fibril formation...
  67. ncbi request reprint Probing copper2+ binding to the prion protein using diamagnetic nickel2+ and 1H NMR: the unstructured N terminus facilitates the coordination of six copper2+ ions at physiological concentrations
    Christopher E Jones
    School of Biological Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS, UK
    J Mol Biol 346:1393-407. 2005
    ..The structure of the Cu/Ni complexes is discussed in terms of the implications for prion protein function and disease...
  68. pmc Metal imbalance and compromised antioxidant function are early changes in prion disease
    Alana M Thackray
    Centre for Veterinary Science, Madingley Road, University of Cambridge, Cambridge CB3 0ES, U K
    Biochem J 362:253-8. 2002
    ..We postulate that alterations in trace-element metabolism as a result of changes in metal binding to PrP are central to the pathological modifications in prion disease...
  69. pmc An aggregation-specific enzyme-linked immunosorbent assay: detection of conformational differences between recombinant PrP protein dimers and PrP(Sc) aggregates
    Tao Pan
    Institute of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44107 1712, USA
    J Virol 79:12355-64. 2005
    ..Finally, the principle of the aggregate-specific ELISA we have developed may be applicable to other diseases caused by abnormal protein aggregation, such as Alzheimer's disease or Parkinson's disease...
  70. ncbi request reprint Plasminogen activation is stimulated by prion protein and regulated in a copper-dependent manner
    Vincent Ellis
    School of Biological Sciences, University of East Anglia, Norwich, UK
    Biochemistry 41:6891-6. 2002
    ....
  71. ncbi request reprint Prion protein is ubiquitinated after developing protease resistance in the brains of scrapie-infected mice
    Shin Chung Kang
    Institute of Pathology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA
    J Pathol 203:603-8. 2004
    ..Whether this post-translational modification and the impairment of proteasome function are pivotal events in the pathogenesis of prion diseases remains to be determined...
  72. pmc Detection of bovine spongiform encephalopathy, ovine scrapie prion-related protein (PrPSc) and normal PrPc by monoclonal antibodies raised to copper-refolded prion protein
    Alana M Thackray
    Centre for Veterinary Science, Department of Clinical Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK
    Biochem J 370:81-90. 2003
    ..In addition, this analysis allowed one to make a distinction between bovine spongiform encephalopathy ('BSE') and scrapie PrPSc) isolates from experimentally infected sheep on the basis of their different electrophoretic mobilities...
  73. ncbi request reprint Copper chelation delays the onset of prion disease
    Einar M Sigurdsson
    Department of Psychiatry, New York University School of Medicine, Millhouser Labs, Room HN418, 560 First Avenue, New York, NY 10016, USA
    J Biol Chem 278:46199-202. 2003
    ..Overall, these findings indicate that copper levels can influence the conformational state of PrP, thereby enhancing its infectivity, and this effect can be attenuated by chelator-based therapy...
  74. ncbi request reprint High affinity copper binding by stefin B (cystatin B) and its role in the inhibition of amyloid fibrillation
    Eva Zerovnik
    Department of Biochemistry and Molecular Biology, Jozef Stefan Institute, Ljubljana, Slovenia
    FEBS J 273:4250-63. 2006
    ..We show that copper binding inhibits the amyloid fibril formation and, to a lesser degree, the initial aggregation. Similarities to and differences from other copper binding amyloidogenic proteins are discussed...
  75. ncbi request reprint Real-time kinetics of discontinuous and highly conformational metal-ion binding sites of prion protein
    Carina Treiber
    Institut für Chemie Biochemie, Freie Universitat Berlin, Thielallee 63, 14195 Berlin, Germany
    J Biol Inorg Chem 12:711-20. 2007
    ..His111 is essential for Co(II) binding, whereas His96 is more important than His111 for binding of Cu(II)...
  76. ncbi request reprint Deconvoluting the Cu2+ binding modes of full-length prion protein
    Mark Klewpatinond
    School of Biological and Chemical Sciences, Queen Mary, University of London, Mile End Road, London, E1 4NS, United Kingdom
    J Biol Chem 283:1870-81. 2008
    ..The affinity and number of Cu(2+) binding sites support the suggestion that PrP could act as a sacrificial quencher of free radicals generated by copper redox cycling...
  77. doi request reprint Raman optical activity and circular dichroism reveal dramatic differences in the influence of divalent copper and manganese ions on prion protein folding
    Fujiang Zhu
    WestCHEM, Department of Chemistry, University of Glasgow, Glasgow G12 8QQ, United Kingdom
    Biochemistry 47:2510-7. 2008
    ..The very different influence of Cu2+ and Mn2+ ions on prion protein structure may originate in the different stability constants and geometries of their complexes...
  78. ncbi request reprint Copper-dependent co-internalization of the prion protein and glypican-1
    Fang Cheng
    Department of Experimental Medical Science, Division of Neuroscience, Glycobiology Group, Lund University, Lund, Sweden
    J Neurochem 98:1445-57. 2006
    ..These results indicate that the interaction between glypican-1 and Cu2+-loaded prion protein is required both for co-internalization and glypican-1 self-pruning...
  79. ncbi request reprint Prion protein does not redox-silence Cu2+, but is a sacrificial quencher of hydroxyl radicals
    Rebecca C Nadal
    School of Biological and Chemical Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS, UK
    Free Radic Biol Med 42:79-89. 2007
    ..This suggests that PrP does not affect levels of hydroxyl radical production via Fentons cycling, but the radicals cause highly localized chemical modification of PrP(C)...
  80. pmc NMR characterization of the pH 4 beta-intermediate of the prion protein: the N-terminal half of the protein remains unstructured and retains a high degree of flexibility
    Christopher E Jones
    School of Biological and Chemical Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS, UK
    Biochem J 401:533-40. 2007
    ..The loss of signals from the C-terminus can be attributed to line broadening due to an increase in the molecular size of the oligomer or exchange broadening in a molten-globule state...
  81. ncbi request reprint Generation of hydrogen peroxide from mutant forms of the prion protein fragment PrP121-231
    Stuart Turnbull
    Department of Biological Sciences, University of Lancaster, Lancaster LA1 4YQ, UK
    Biochemistry 42:7675-81. 2003
    ..Thus, one effect of these (and possibly other) prion mutations could be production of a particularly toxic form of the prion protein, with an enhanced capacity to induce oxidative damage, neurodegeneration, and cell loss...
  82. ncbi request reprint Anterograde axonal transport of chicken cellular prion protein (PrPc) in vivo requires its N-terminal part
    Rafal Butowt
    Department of Physiology and Cell Biology, University of Nevada, School of Medicine, Reno, Nevada, USA
    J Neurosci Res 85:2567-79. 2007
    ..These data indicate that the N-terminal half of chicken PrP(c) contains the necessary information to drive the internalization and subsequent sorting of extracellular PrP(c) in RGCs soma into the anterograde axonal transport pathway...
  83. pmc Autonomic neurotransmitters modulate immunoglobulin A secretion in porcine colonic mucosa
    Lisa D Schmidt
    Department of Veterinary and Biomedical Sciences, University of Minnesota, 1988 Fitch Avenue, St Paul, Minnesota 55108 6010, USA
    J Neuroimmunol 185:20-8. 2007
    ..Acetylcholine and norepinephrine, acting respectively through muscarinic cholinergic and alpha-adrenergic receptors in the colonic mucosa, stimulate sIgA secretion and may enhance mucosal defense in vivo...
  84. ncbi request reprint Predominance of delta-opioid-binding sites in the porcine enteric nervous system
    DeWayne Townsend
    Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Minnesota, St Paul, Minnesota 55108 6010, USA
    J Pharmacol Exp Ther 300:900-9. 2002
    ..These results indicate that delta-OPRs predominate in the porcine enteric nervous system with a more circumscribed expression of kappa- and mu-OPRs...
  85. ncbi request reprint Novel inhibitors of bacterial cytokinesis identified by a cell-based antibiotic screening assay
    Neil R Stokes
    Prolysis Ltd, Oxford University Begbroke Science Park, Oxfordshire, OX5 1PF, United Kingdom
    J Biol Chem 280:39709-15. 2005
    ..They have provided new insight into cytokinesis in bacteria and offer important reagents for further studies of the cell division machinery...
  86. pmc Immunization delays the onset of prion disease in mice
    Einar M Sigurdsson
    Department of Psychiatry, New York University School of Medicine, New York, New York 10016, USA
    Am J Pathol 161:13-7. 2002
    ..The increase in the incubation period closely correlated with the anti-prion protein antibody titer. This promising finding suggests that a similar approach may work in humans or other mammalian species at risk for prion disease...
  87. ncbi request reprint Active bicarbonate-dependent secretion evoked by 5-hydroxytryptamine in porcine ileal mucosa is mediated by opioid-sensitive enteric neurons
    Benedict T Green
    Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Minnesota, 1988 Fitch Avenue, St Paul, MN 55108 6010, USA
    Eur J Pharmacol 451:185-90. 2002
    ..These results suggest that 5-HT stimulates HCO(3)(-)-dependent ion transport through a mechanism involving prostanoids and an enteric neural pathway modulated by opioids...
  88. ncbi request reprint Adrenocorticotrophic hormone modulates Escherichia coli O157:H7 adherence to porcine colonic mucosa
    Kristin L Schreiber
    Graduate Program in Neuroscience, University of Minnesota, Minnesota 55108 6010, USA
    Stress 8:185-90. 2005
    ..Moreover, ACTH7-38 decreased EHEC adherence in the absence of ACTH. These results suggest that ACTH acts via melanocortin receptors located on enteric nerves to enhance mucosal adherence of EHEC...
  89. ncbi request reprint Cell death and autophagy in prion diseases (transmissible spongiform encephalopathies)
    Paweł P Liberski
    Department of Molecular Pathology and Neuropathology, Chair of Oncology, Medical University of Lodz, Czechosłowacka Str 8 10, PL 92 216 Lodz, Poland
    Folia Neuropathol 46:1-25. 2008
    ..On the basis of ultrastructural studies, we suggest that autophagy may play a major role in transmissible spongiform encephalopathies and may even participate in the formation of spongiform change...
  90. pmc Genetic manipulation of intraspinal plasticity after spinal cord injury alters the severity of autonomic dysreflexia
    Adrian A Cameron
    Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, Kentucky 40536, USA
    J Neurosci 26:2923-32. 2006
    ..These results demonstrate that site-directed genetic manipulation of axon guidance molecules after complete spinal cord injury can alter endogenous circuitry to modulate plasticity-induced autonomic pathophysiology...
  91. ncbi request reprint Copper-dependent generation of hydrogen peroxide from the toxic prion protein fragment PrP106-126
    Stuart Turnbull
    Department of Biological Sciences, Lancaster University, Lancaster LA1 4YQ, UK
    Neurosci Lett 336:159-62. 2003
    ....
  92. ncbi request reprint Food supply controls the body condition of a migrant bird wintering in the tropics
    David R Brown
    Department of Ecology and Evolutionary Biology, Tulane University, 310 Dinwiddie Hall, New Orleans, LA 70118, USA
    Oecologia 149:22-32. 2006
    ..Moreover, since these effects were observed during the late non-breeding period, when individuals are preparing to migrate, we infer that food availability likely initiates carry-over effects...