David R. Brown, B.Sc., M.Sc. Ph.D.

email: bssdrb@bath.ac.uk

Professor of Biochemistry


RESEARCH INTO NEURODEGENERATIVE DISORDERS



The Group.

My group currently has the following members:
 
Dr. Josephine Wright
Paul Davies
Sarah Fontaine
Dima Moualla
Scarlet Wang


 
 
 
 

My group in the Department of Biology and Biochemistry is concerned with Molecular Neuroscience. Our major focus is related to the field of prion diseases. We also work on the interaction of neurones and glia with special emphasis on astrocyte protection of neurones from glutamate toxicity. I am currently supported by a Fellowship from the BBSRC. Originally, my background was in biochemistry and physiology. My Ph.D. in Syndey University gave me a solid background in neuroscience and some experience with electrophysiology. However my main technical interests are in molecular biology biochemistry and cell culture. My interest in prion protein and prion disease began in 1993 while I was working in the German University town of Goettingen. I ran a group in Cambridge for four years (1997-2001) before moving to the University of Bath.
 

Current Research Interests Related to Pion Protein and other Proteins associated with Neurodegeneration

1. The function of the prion protein, alpha-synuclein and Amyloid Precursor Protein

2. Neurodegeneration in cell culture models 

3. The interaction of metals and proteins

4. Aggregation of prion protein or alpha-synuclein

5. Factors altering susceptibility to prion infection in culture

6. Regulation of gene transcription for the Prnp gene or genese for alpha- an beta- synclein. Also regulation of secretase transcription.
 

Publications by David Brown related to the Prion Protein or Prion Disease.
 

1.  Brown, D. R., Herms, J. and Kretzschmar, H. A. (1994) Mouse cortical cells lacking cellular PrP survive in culture with a neurotoxic PrP fragment. Neuroreport 5: 2057-2060.

2. Brown, D. R., Schmidt, B. and Kretzschmar, H. A (1996) Role of microglia and host prion protein in neurotoxicity of a prion protein fragment. Nature  380: 345-347.

3. Brown, D. R., Schmidt, B. and Kretzschmar, H. A (1996) A neurotoxic prion protein fragment enhances proliferation of microglia but not astrocytes in culture. Glia  18: 59-67.

4.  Kretzschmar, H. A., Giese, A., Brown, D. R., Herms, J. W., Schmidt, B. and Groschup, M. H. (1996) Cell Death in Prion Disease in   Transmissible Subacute Spongiform Encephalopathies: Prion Diseases. Ed., Court, L. and Dodet, B., Elsevier, Paris, pp: 97-106.

5.  Kretzschmar, H. A., Giese, A., Brown, D. R. Herms, J. W.,  Keller, B. Schmidt, B. Groschup, M. (1997) Cell Death in Prion Disease. J. Neural Transm. [Suppl] 50: 191-210

6. Brown, D. R. and Kretzschmar, H. A. (1997) Microglia and prion disease: a review. Histol. Histopathol.  12: 883-892.

7. Brown, D. R., Herms, J. W., Schmidt, B. and Kretzschmar, H. A (1997) Different requirements for the neurotoxicity of fragments of PrP and ß-amyloid.
  Euro. J. Neurosci.  9: 1162-1169.

8. Herms, J. W., Madlung, A., Brown, D. R. and Kretzschmar, H. A. (1997) Increase of intracellular free Ca2+ in microglia activated by prion protein fragment. Glia  21: 253-257.

9. Brown, D. R., Schulz-Schaeffer, W. J., Schmidt, B. and Kretzschmar, H. A (1997) Prion protein-deficient cells show altered response to oxidative stress due to decreased SOD-1 activity.  Exp. Neurol.  146: 104-112.

10. Brown, D. R., Qin, K., Herms, J. W., Madlung, Manson, J., Strome, R., Fraser, P. E. Kruck, T., A., von Bohlen, A., Schulz-Schaeffer, W., Giese, A., Westaway, D. and Kretzschmar, H. (1997) The cellular prion protein binds copper in vivo. Nature  390:684-687.

11. Brown, D. R., Schmidt, B. and Kretzschmar, H. A. (1997) Expression of prion protein in PC12 is enhanced by exposure to oxidative stress. Int. J. Dev. Neurosci.   15: 961-972.

12. Kretzschmar, H. A., Windl, O., Brown, D. R., Giese, A., Schulz-Schaeffer, W. and Herms, J. (1998) Molecular pathology of transmissible spongiform encephalopathies. Neurosci. News  1: 17-25.

13. Brown, D. R., Schmidt, B., Groschup, M. H. and Kretzschmar, H. A. (1998) Prion protein expression in muscle cells and toxicity of a prion protein fragment. Eur. J. Cell Biol.  75: 29-37.

14. Brown, D. R., Schmidt, B. and Kretzschmar, H. A. (1998) A prion protein fragment interacts with PrP-deficient cells. J. Neurosci. Res.  52: 260-267.

15. Brown, D. R., Schmidt, B. and Kretzschmar, H. A. (1998) A prion protein fragment primes type 1 astrocytes to proliferation signals from microglia. Neurobiol. Disease  4: 410-422.

16. Brown, D. R., Schmidt, B. and Kretzschmar, H. A. (1998) Effects of copper on survival of prion protein knockout neurones and glia. J. Neurochem.  70, 1686-1693.

17. Brown, D. R., Besinger, A., Herms, J. W. and Kretzschmar, H. A. (1998)  Microglial expression of the prion protein. Neuroreport    9, 1425-1429.

18. Giese, A., Brown, D. R., Groschup, M. H., Feldmann, C., Haist, I. and Kretzschmar, H. A. (1998) Role of microglia in neuronal cell death in prion disease. Brain Pathol. 8, 449-457.

19. Brown, D. R., Pitschke, M., Riesner, D. and Kretzschmar, H. A. (1998) Cellular effects of a neurotoxic prion protein peptide are related to its b-sheet content. Neurosci. Res. Comm.  23: 119-128.

20. Brown, D. R. (1998) Toxicity of a b-amyloid peptide fragment in neurones and glia with reduced APP expression. Alzheimer’s Rep. 1, 223-231.

21. Brown, D. R. and Besinger, A. (1998) Prion protein expression and superoxide dismutase activity. Biochem. J.  334, 423-429.

22. Brown, D. R.  (1998) Prion protein-overexpressing cells show altered response to a neurotoxic prion protein peptide J. Neurosci. Res.  54, 331-340.

23. Brown, D. R. and Mohn, C. M. (1999) Astrocytic glutamate uptake and prion protein expression. Glia  25, 282-292.

24. Wong, B.-S., Wang, H., Brown, D. R. and Jones, I. M. (1999) Selective oxidation of methionine residues in prion proteins. Biochem. Biophys. Res. Comm. 279, 352-355.

25. Brown, D. R. (1999) Prion protein peptide neurotoxicity can be mediated by astrocytes. J. Neurochem. 73, 1105-1113.

26. McHattie, S. J., Brown, D. R. and Bird, M. M. (1999) Cellular uptake of the prion protein fragment PrP106-126 in vitro.  J. Neurocytol.  28, 145-155.

27. Bürkle, A., Kretzschmar, H. A. and Brown, D. R. (1999) Poly(ADP-ribose) immunostaining to detect apoptosis induced by a neurotoxic fragment of prion protein. Histochem. J.   31, 711-716.

28. Brown, D. R. (1999)  Prion protein expression aids cellular uptake and veratridine-induced release of copper. J. Neurosci. Res. 58, 717-725.

29. Brown, D.R., Wong, B.S., Hafiz, F., Clive, C., Haswell, S. and Jones, I.M. (1999) Normal prion protein has an activity like that of superoxide dismutase. Biochem. J. 344, 1-5.

30. Brown, D. R. (1999) Comment on: Neurotoxicity of prion protein peptide 106-126 not confirmed. FEBS Lett. 460, 559-560.

31. Brown, D. R. (2000) Prion protein peptides: Optimal toxicity and peptide blockade of toxicity. Mol. Cell Neurosci. 15, 66-78.

32. Brown, D. R. (2000) Altered toxicity of the prion protein peptide PrP106-126 carrying the A117V mutation. Biochem. J. 346, 784-791.

33. Wong, B.-S., Clive, C., Haswell, S. J., Jones, I. M. and Brown, D. R. (2000) Copper has differential effect on prion protein with polymorphism of position 129. Biochem Biophys. Res. Comm. 269, 726-731.

34. Brown, D. R., Hafiz, F., Glasssmith, L. L., Boon-Seng Wong, B.-S., Jones, I. M., C Clive, C., and Haswell, S. J. (2000) Consequences of manganese replacement of copper for prion protein function and proteinase resistance. EMBO J. 19, 1180-1186.

35. Brown, D. R. , Iordanova, I. M., Wong, B.-S., Vénien-Bryan, C., Hafiz, F., Glasssmith, L. L., Sy, M.-S. , Gambetti, P.,  Jones, I. M., Clive, C. and Haswell, S. J. (2000) Functional and structural differences between the prion protein from two alleles prnpa and prnpb of mouse. Eur. J. Biochem. 267, 2452-2459.

36. Hafiz, F. and Brown, D. R. (2000) A model for the mechanism of astrogliosis in prion disease. Mol. Cell Neurosci.  16, 221-232.

37. Post, K., Brown, D. R., Groschup, M., Kretzschmar H. and Riesner, D. (2000) Neurotoxicity but not infectivity of prion proteins can be induced reversibly in vitro. Arch. Virol. Suppl.16, S265-S273.

38. Wong, B.-S., Pan, T., Liu, T., Li, R., Jones, I. M., Gambetti, P., Petersen, R. B., Brown, D. R. and Sy, M.-S. (2000) Prion disease: a loss of anti-oxidant function? Biochem. Biophys. Res. Comm. 275, 249?252.

39. Wong, B.-S., Vénien-Bryan, C., Williamson, R. A., Burton , D. R., Gambetti, P., Sy, M.-S., Brown, D. R., and Jones, I. M. (2000) Copper refolding of Prion Protein. Biochem. Biophys. Res. Comm. 276, 1217-1224.

40. Brown, D. R. (2000) PrPSc-like prion protein peptide inhibits the function of cellular prion protein. Biochem. J.  352, 511-518.

41. Brown, D. R. (2001) Prion protein peptide: agents of death for neurons. in  Molecular Pathology of Prion Diseases. Ed. Baker, H. Humana Press   Totowa, New Jersey, USA pp.51-70.

42. Brown, D. R. and Jones, I. M. (2001) A function for the prion protein? in  Molecular Pathology of Prion Diseases. Ed. Baker, H. Humana Press   Totowa, New Jersey, USA pp:31-50..

43. Brown, D. R., Clive, C. and Haswell, S. J. (2001) Anti-oxidant activity related to copper binding of native prion protein. J. Neurochem. 76, 69-76.

44. Brown, D. R. (2001) Microglia in Prion Disease. Microscop. Res. Tech. 54, 71-80.

45. Wong, B.-S. Liu, T., Ruliang Li, R., Pan, T., Petersen, R. B., Smith, M. S. Gambetti, P., Perry, G., Manson, J.,. Brown, D. R.  and Sy, M.-S.  (2001) Increased levels of oxidative stress markers detected in the brains of mice devoid of prion protein. J. Neurochem. 76, 565-572.

46. Brown, D. R. (2001) Prion and prejudice: normal protein at the synapse. Trends Neurosci. 24, 85-90.

47. Brown, D. R. (2001) Copper and prion disease. Brain Res. Bull. 55, 165-173.

48. Wong, B.-S., Liu, T., Paisley, D., Li, R.,  Pan, T. Chen, S. G., Perry, G., Petersen, R. B., Smith, M. A., Melton, D. W., Gambetti, P., Brown, D. R. and  Sy, M.-S. (2001) Induction of HO-1 and NOS in doppel-expressing mice devoid of PrP: Implications for Doppel function. Mol. Cell Neurosci. 17, 768-775.

49. Brown, D. R. (2001) BSE: A post-industrial disease?Chem. Indust.  3, 73-76.

50. Brown D. R. (2001) BSE did not cause variant CJD: An alternative cause related to post-Industrial environmental contamination. Med. Hypoth. 57, 555-560. 

51. Brown, D. R. (2001) An alternative cause for BSE and variant CJD related to post-industrial environmental contamination. World Leather  14, 33-38.

52. Wong, B.-S., Chen, S. G., Colucci, M., Xie, Z., Pan, T., Liu, T., Li, R., Gambetti, P., Sy, M.-S. and Brown, D. R. (2001) Aberrant  metal binding by prion protein in human prion disease. J. Neurochem.  78, 1400-1408.

53. Wong, B.-S., Brown, D. R. and Sy, M.-S. (2001) A yin-yang role for metals in prion disease. Panminerva Med. 43, 283-287.

54. Wong, B.-S., Brown, D. R., Pan, T., Whiteman, M., Liu, T., Bu, X., Li, R., Gambetti, P., Olesik, J., Rubinstein, R. and  Sy, M.-S. (2001) Oxidative impairment in scrapie-infected mice is associated with brain metal perturbations and altered ani-oxidantion activities. J. Neurochem.  79, 689-698.

55. Daniels, M., Cereghetti, G. M. and Brown, D. R. (2001) Toxicity of novel C-terminal prion protein fragments and peptides harbouring disease-related C-terminal mutations.Eur. J. Biochem. 268, 6155-6164.

56. Daniels, M. and Brown, D. R. (2002) Purification and preparation of prion protein: The synaptic superoxide dismutase. Meth. Enzymol. 349, 258-267.

57. Brown, D. R. (2002) Prion protein: A synaptic cuproprotein in  Handbook of Copper Pharmacology and Toxiciology Ed. E. Massaro, Humana Press, Totowa, New Jersey, USA. pp115-129.

58. Brown, D. R., Nicholas, R. St. J., and Canevari, L. (2002) Lack of prion protein expression results in a neuronal phenotype sensitive to stress. J. Neurosci. Res. 67, 211-224.

59. Wong, B.-S., Sy, M.-S. and Brown, D. R. (2002) Prion-like doppel protein expression correlates with heme oxygenase  and nitric oxide synthase induction. Heme Oxygenase in Biology and Medicine.  Ed. N.G Abraham, Plenum Press, New York, USA pp. 423-430.

60. Thackray, A. M., Knight, R.,  Haswell, S. J.,  Bujdoso, R. and Brown, D. R. (2002) Metal imbalance and compromised antioxidant function are early changes in prion disease.  Biochem. J. 362, 253-258.

61. Brown, D. R. (2002) Molecular advances in understanding inherited prion diseases. Mol. Neurobiol. 25, 287-302.

62. Brown, D. R. (2002) Don’t lose sleep over prions: role of prion protein in sleep regulation. Neuroreport  13, A1.

63. Brown, D. R. (2002) Mayhem of the multiple mechanisms: Modelling neurodegeneration in prion disease. J. Neurochem. 82, 209-215.

64. Sigurdsson, E. M., Brown, D. R., Daniels, M., Kascsak, R. J., Kascsak, R., Carp, R., Meeker, H. C., Frangione, B. and Wisniewski, T. (2002) Immunization delays the onset of prion disease in mice. Am. J. Pathol. 161, 13-17.

65. Brown, D. R.  and Sassoon, J. (2002) Copper dependent functions for the prion protein. Molec. Biotech. 22, 165-178.

66. Ellis, V., Daniels, M., Misra, R. and Brown, D. R. (2002) Plasminogen activation is stimulated by prion protein and regulated in a copper-dependent manner. Biochemistry  41, 6891-6896.

67. Wisniewski, T., Brown D. R. and Sigurdsson, E. M. (2002) Therapeutics in Alzheeimer’s and prion disease. Biochem. Soc. Trans. 30, 574-578.

68. Brown, D. R. (2002) Copper and prion disease. Biochem. Soc. Trans. 30, 742-745.

69. Turnbull, S., Tabner, B. J., Brown, D. R. and Allsop, D. (2003) Copper-dependent generation of hydrogen peroxide from the toxic prion protein fragment PrP106-126. Neurosci. Lett.  336, 159-162.

70. Thackray, A. M., Madec, J. Y., Wong, E., Morgan-Warren, R., Brown, D. R., Baron, T. and Bujdoso, R. (2003) Detection of BSE, ovine scrapie PrP Sc and normal PrP c by monoclonal antibodies raised to copper-refolded prion protein. Biochem J. 370, 81-90.

71. Haywood, S. and Brown, D. R. (2003) Transmissible spongiform encephalopathies: a revaluation and possible role of environmental factors in prion diseases. Vet. Times, 33:2, 8-10.

72. Sassoon, J. and Brown, D. R.  (2003) Copper and prion disease. Metal Ions and Neurodegeneration  Ed. Zatta, P., World Scientific, New Jersey. Pp. 279-306.

73. Cui, T.,  Holme, A., Sassoon, J. and Brown, D.R. (2003) Analysis of doppel protein toxicity. Mol. Cell Neurosci. 23, 144-145.

74. Wong, B. S., Li, R., Sassoon, J.,  Kang, S.-C.,  Liu, T., Pan, T. Wisniewski, T.,  Brown, D. R. and Man-Sun Sy. M.-S. (2003) Mapping the antigenicity of copper-treated cellular prion protein with the scrapie isoform. Cell Molec. Life Sci. 60, 1224-1234.

75. Turnbull, S.,  Tabner, B. J., Brown, D. R. and Allsop, D. (2003) Generation of hydrogen peroxide from mutant forms of the prion protein fragment PrP121-231 Biochemistry  42, 7675-7681.

76. Liberski, P. P., Sikorska, B., Bratosiewicz-Wlsik, J., Walic, A., Brown, P., and Brown, D. R. (2003) Exuberant cellular reaction of the optic nerves in experimental Creutzfeldt-Jakob disease. Acta Neurobiol. Exp. 63, 309-318.

77. Brown, D. R.  and Sinclair, K. (2003) Deer slaughter outrage. Vet. Times 33:14, 18.

78. Holme, A., Daniels, M., Sassoon, J. and Brown, D. R.  (2003) A novel method of generating neuronal cell lines from gene-knockout mice to study prion protein membrane orientation. Eur. J. Neurosci. 18, 571-579.

79. Turnbull, S., Tabner, B. J., Brown, D. R. and Allsop, D. (2003) Quinacrine acts as an antioxidant and reduces the toxicity of the prion peptide PrP106-126. Neuroreport  14, 1743-1745.

80. Cui, T., Daniels, M., Wong, B. S., Li, R., Sy, M.-S., Sassoon, J. and Brown, D. R. (2003) Mapping the functional domain of the prion protein. Eur. J. Biochem. 270, 3368-3376.

81. Brown, D. R. (2003)  Conformational exposure: a new handle on prions. Lancet  362, 929-930.

82. Brown, D. R.  (2003) Prion protein expression modulates neuronal copper content. J. Neurochem . 87, 377-385.

83. Sigurdsson, E. M., Brown, D. R., Alim, M. A.,  H. Scholtzova, H., Carp, R. H.C. Meeker, H. C., Prelli, F., Frangione, B.,  Wisniewski, T. (2003) Copper chelation delays the onset of prion disease. J. Biol. Chem. 278, 46199-46202.

84. Brown, D. R. and Sassoon, J. (2004) Role of glia in prion disease. Advance. Mol. Cell Biol. 31, 1085-1104.

85. Brown, D. R., Guantieri, V., Grasso, G.,  Impellizzeri, G.,  Pappalardo, G. and Rizzarelli, E. (2004) 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. J. Inorgan. Biochem.  98, 133-143.

86. Thompsett, A. R. and Brown, D. R. (2004) A functional role for a copper binding prion protein. Prions and Prion Diseases: Current Perspectives. Ed. Telling, G. pp.1-40.  Horizon Bioscience, Wymondham, UK.

87. Sassoon, J. and Brown, D. R. (2004) Neuronal death in prion disease. (In Press).

88. Sassoon, J., Banks, F. and Brown, D. R. (2004) Neurotoxicity and prion disease.  In Excitotoxicity in Neurological Disease, New Therapeutic Challenge  Ed. Ferrarese, C. and Beal, M. F. pp. 265-283 Kluwer, Hingham USA .

89. Sassoon, J., Sadowski, M., Wisniewski, T. and Brown, D. R. (2004). Therapeutics and prion disease: Can immunisation or drugs be effective? Mini-Rev. Med. Chem. (In Press).

90. Sassoon, J., Daniels, M. and Brown, D. R. (2004) Astrocytic regulation of NMDA receptor subunit composition modulates the toxicity of prion peptide PrP106-126. Mol. Cell Neurosci. 25, 181-191.

91. Brown, D. R. (2004) Role of the prion protein in copper turnover in astrocytes. Neurobiol. Dis. 15, 534-543.

92. Kang, S-C., Brown, D. R. Whiteman, M.,  Li, R., Pan, T., Perry, G., Thomas Wisniewski, T.,  Sy, M.-S., and Wong, B.-S. (2004) Prion protein is ubiquitinated after developing protease resistance in the brains of scrapie-infected mice. J. Pathol. 203, 603-608.

93. Brown, D.R. (2004) Metallic Prions. Biochem. Soc. Symp.  71, 193-202.

94. Calissano, M., Ensor, E., Irshad, S., Brown, D. R. and Latchman, D. S. (2004) Transcriptional regulation of prion protein like doppel by the Brn-3a and Brn-3b transciptional factors. Neuroreport  15, 483-486.

95. Brown, D. R. and Kozlowski, H. (2004) Biological inorganic and bioinorganic chemistry of neurodegeneration based on prion and Alzheimer diseases. Dalton Trans. 13, 1907-1917.

96. Jones, C. E., Abdelraheim, S. R., Brown, D. R.  and Viles, J. H. (2004) Preferential copper2+ coordination by His96 and His111 induces b-sheet formation in the unstructured amyloidogenic region of the prion protein. J. Biol. Chem. 279, 32018-32027.

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97. Lekishvili, T., Sassoon, J., Thompsett, A. R., Green, A., Ironside, J. W. and Brown, D. R. (2004) BSE and vCJD cause disturbance to uric acid levels. Exp. Neurol. 190, 233-244.

98. Sellarajah, S., Lekishvili, T., Bowring, C., Thompsett, A. R., Rudyk, Birkett, C. R., Brown, D. R. and Gilbert, I. H. (2004) Synthesis of analogues of congo red and evaluation of their anti-prion activity. J. Med. Chem. 47, 5515-5534.

99. Tsenkova, R. N., Iordinova, I. K., Toyoda K., and Brown, D. R. (2004) Prion protein fate governed by metal binding. Biochem. Biophys. Res. Comm. 325, 1005-1012.

100. Jones, C. E., Klewpatinond, M., Abdelraheim, S. R., Brown, D. R. and Viles, J. H. (2005) Probing copper2+ binding to the prion protein using diamagnetic nickel2+ and 1H NMR: Six Cu2+ ions bind at physiological concentrations. J. Mol. Biol. 346, 1393-1407.

101. Sassoon, J., Sadowski, M., Wisniewski, T. and Brown, D. R. (2005). Therapeutics and prion disease: Can immunisation or drugs be effective? Mini-Rev. Med. Chem. 5, 361-366.

102. Goñi, F., Knudsen, E., Schreiber, F., Scholtzova, H., Pankiewicz, J., Carp, R., Meeker, H. C., Brown, D. R., Sy, M.-S., Chabalgoity, J. A., Sigurdsson, E. M. and Wisniewski, T. (2005) Mucosal vaccination delays or prevents prion infection via an oral route. Neuroscience  133, 413-421.

103. Haigh, C. L., Edwards, K. and Brown, D. R. (2005) Copper binding is the governing determinant of prion protein turnover. Mol. Cell Neurosci.  30, 186-196.

104. Pan, T., Chang, B., Wong, P. Li, C. Li, R. Kang, S.-C., Robinson, J. D., Thompsett, A. R., Po, T., Yin,  S., Barnard, G., McConnell. I., Brown, D. R., Wisniewski, T., Sy, M.-S. (2005) An aggregation-specific enzyme-linked immunosorbent assay: Detection of conformational differences between recombinant PrP protein dimers and PrPSc aggregates: J. Virol. 79, 12355-123464

105. Brown, D. R. (2005) A field on fire: the biochemistry of mad cows. The Biochemist, 27, 6-8.

106. Brown. D. R. (2005) The use of peptides to pick up prions: protection or poison? Expert  Opin. Therap. Patents, 15, 1287-1290.

107. Thompsett, A. R., Abdelraheim, S. R., Daniels, M. and Brown, D. R. (2005) High affinity binding between copper and full-length prion protein  identified by two different techniques. J. Biol. Chem. 280 42750-42758.

108. Brown, D. R. (2005) Neurodegeneration and oxidative stress: prion disease results from loss of antioxidant defence.Folia Neuropathologica, 43, 229-243.

109. Butowt, R., Abdelraheim, S., Brown, D. R. and von Bartheld, C. S. (2006) Anterograde axonal transport of exogenous cellular isoform of prion protein in the chick visual system.Mol. Cell Neurosci.  31, 97-108.

110. Brown, D. R.  (2006) Metallic prions: Mining the core of transmissible spongiform encephalopathies. Met. Ions Life Sci. 1, 89-114.

111. Abdelraheim, S. R., Kralovicova, S.and Brown, D. R. (2006) Hydrogen peroxide cleavage of the prion protein generates a fragment able to initiate polymerisation of full length prion protein. Int. J. Biochem. Cell Biol. 38, 1429-1440.

112. Haigh, C. L. and Brown, D. R. (2006) Prion protein reduces both oxidative and non-oxidative copper toxicity. J. Neurochem. 98, 677-689.

113. Cheng, F., Lindqvist, J., Haigh, C. L., Brown, D. R. and Mani, K. (2006) Copper-dependent co-internalization of the prion protein and glypican-1. J. Neurochem. 98, 1445-1457.

114. Haigh, C. L. and Brown, D. R. (2006) Regulation of prion protein expression: A potential site for therapeutic intervention in the transmissible spongiform encephalopathies. Int. J. Biomed. Sci. 2, 315-323.

115. O'sullivan, D. B., Jones, C. E., Abdelraheim, S. R., Thompsett, A. R., Brazier, M. W., Toms, H., Brown, D. R. and  Viles, J. H.  (2007)  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. Biochem. J. 401, 533-540.

116. Nadal, R. C., Abdelraheim, S. R., Brazier, M. W., Rigby, S. E., Brown, D. R. and Viles, J. H.  (2007) Prion protein does not redox-silence Cu(2+), but is a sacrificial quencher of hydroxyl radicals. Free Radic Biol Med. 42, 79-89.

117.  Butowt, R., Davies, P. and Brown, D. R. (2007) Anterograde axonal transport of chicken cellular prion protein (PrPc) in vivo requires its N-terminal part. J. Neurosci. Res. 85, 2567-2579.

118. Hesketh, S., Sassoon, J., Knight R., Hopkins, J. and Brown D. R. (2007) Elevated manganese levels in blood and CNS Occur prior to onset of clinical signs in scrapie and BSE. J. Animal Sci. 85: 1596-1609.

119. Haigh, C. L., Wright, J. A. and Brown, D. R. (2007) Regulation of prion protein expression by non coding regions of the Prnp gene. J. Mol. Biol. 368, 915-927.

120. Uppington, K. M. and Brown D. R. (2007) Modelling neurodegeneration in prion disease - applications for drug development. Expert Opin. Drug Discov. 2, 777-788.

121. Treiber, C., Thompsett, A. R., Pipkorn, R., Brown, D. R. and Multhaup G. (2007) Real-time kinetics of discontinuous and highly conformational metal-ion binding sites of prion protein. J. Biol. Inorg. Chem. 12, 711-720.

122. Thompsett, A. R. and Brown, D. R.  (2007) Dual polarisation interferometry analysis of copper binding to the Prion Protein: evidence for two folding states. Biochim. Biophys. Acta 1774,920-927.

123. Webb, S., Lekishvili, T., Loeschner, C., Sellarajah, S., Prelli, F., Wisniewski, T., Gilbert, I. H. and Brown, D. R. (2007) Mechanistic insights into prion curing by novel anti-Prion compounds. J. Virol. 81, 10729-10741.

124. Sellarajah, S., Boussard, C., Lekishvili, T.,  Brown,D. R. and  Gilbert, I. H. (2008) Synthesis and testing of peptides for anti-prion activity. Eur. J. Med. Chem. (In press).

125. Davies, P. and Brown, D. R. (2008) The Chemistry of copper binding to PrP. Is there sufficient evidence to elucidate a role for copper in protein function? Biochem. J. (In press)


Publications by David Brown related to the Alzheimer's or Parkinson's Disease
 
1. Brown, D. R. (1998) Toxicity of a b-amyloid peptide fragment in neurones and glia with reduced APP expression. Alzheimer’s Rep. 1, 223-231.

18. Brown, D. R.  (2007) Copper and amyloid fibril formation. FEBS J. 274, 3755.

19. Brown, D. R.  (2007) Interactions between metals and alpha-synuclein: Function or artefact? FEBS J. 274, 3766-3744.

20. Wright, J. and Brown, D. R. (2007) Alpha-synuclein and its role in metal binding: relevance to Parkinson’s Disease. J. Neurosci. Res. (In Press)


Publications by David Brown on other subjects:

1. Brown, D. R.,  Everett, A. W. and Bennett, M. R. (1989) Compartmental and topographical distributions of axons in nerve to the amphibian (Bufo marinus)  glutaeus muscle. J. Comp Neurol.  284: 231-241.

2. Brown, D. R. and Everett, A. W. (1990) Compartmental and topographical specificity of reinnervation of the glutaeus muscle in adult toad (Bufo marinus). J. Comp Neurol. 292: 363-372.

3. Brown, D. R. and Everett, A. W. (1991) Position and Fibre Type-dependent selectivity by regenerating motor axons in reformation of the topographical projection to the glutaeus muscle in the adult toad (Bufo marinus) J. Comp. Neurol. 309: 495-506.

4.  Brown, D. R. and Kretzschmar, H. A. (1995) Topographical reinnervation of the toad glutaeus muscle by axons of only one spinal nerve. Neuroreport   6:    989-993.

5.  Everett, A. W. and Brown, D. R.(1996) Loss of the position-dependent reinnervation of regenerated  toad (Bufo marinus) glutaeus muscle. J. Comp. Neurol.  366: 293-302.

6. Brown, D. R. and Kretzschmar, H. A. (1998) The glio-toxic mechanism of a-aminoadipic acid on cultured astrocytes.J. Neurocytol.  27: 109-118.

7. Brown, D. R. (1998) A method for long term culture of murine type 2 astrocytes. J. Neurosci. Meth.  79: 161-167.

8. Brown, D. R. (1999) Dependence of neurones on astrocytes in a co-culture system renders neurones sensitive to TGF-b1 induced glutamate toxicity. J. Neurochem.  72, 943-953.

9. Brown, D. R. (1999) Neurones depend on astrocytes in a co-culture system for protection from glutamate toxicity. Mol. Cell. Neurosci. 13, 379-389.

10. Brown, D. R. (2000) Neuronal release of VIP is important to astrocytic protection of neurones from glutamate toxicity. Mol. Cell Neurosci.  15, 465-475.

11. Nicholas, R. St. J., Compston, A. and Brown, D. R. (2001) Inhibition of TNFa induced NF-kB p52 converts the metabolic effects of microglia-derived TNFa on mouse cerebellar neurons to neurotoxicity. J. Neurochem. 76, 1431-1438..

12.  Daniels, M. and Brown D. R. (2001) Astrocytes regulate N-methyl-D-aspartate receptor subunit composition increasing  neuronal sensitivity to excitotoxicity. J. Biol. Chem. 276, 22446-22452.

<>13. Daniels, M. and Brown, D. R. (2002) High extracellular potassium protects against the toxicity of cytosine arabinoside but is not required for the survival of cerebellar granule cells in vitro. Mol. Cell. Neurosci. 19, 281-291.

14. Zerovnik, E., Skerget, K., Tusek, M., Loeschner, C., Brazier, M. W. and Brown, D. R. (2006) High affinity copper binding by stefin B (cystatin B) and its role in inhibiting amyloid formation. FEBS J. 273, 4250-4263.

<>15. Lekishvili, T., Hesketh, S., Brazier, M. W. and Brown, D. R. (2006) Mouse galectin-1 inhibits the toxicity of glutamate by modifying NR1 NMDA receptor expression. Eur. J. Neurosci. 24, 3017-3025.

16. Alderton, A., Davies, P., Illman, K. and Brown, D. R. (2007) Ancient Conserved Domain Protein-1 (ACDP-1) binds copper and modifies its retention in cells. J. Neurochem. 103, 312-321.
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