Medical Hypotheses
Volume 57, Issue 1 , Pages 29-45 , July 2001

Does an ultra violet photooxidation of the manganese-loaded/copper-depleted prion protein in the retina initiate the pathogenesis of TSE?

Received 20 December 2000 ,Accepted 9 January 2001.

References 

    REFERENCES
  1. Bastian, F. CJD and other transmissible spongiform encephalopathies. St Louis, Mosby Year Book, 1991
  2. Collinge J, Palmer MS. Prion Diseases Oxford. Oxford University Press,. 1997;
  3. Purdey M. The UK epidemic of BSE: slow virus or chronic pesticide initiated modification of the prion protein (Parts 1 and 2). Med Hypotheses. 1996;46:429–454
  4. Purdey M. Ecosystems supporting clusters of sporadic TSEs demonstrate excesses of the radical generating divalent cation manganese and deficiencies of antioxidant co factors Cu, Se, Fe, Zn. Does a foreign cation substitution at PrP’s Cu domain initiate TSE?. Med Hypotheses. 2000;54:278–306
  5. Brown D, Hafiz F, Glassmith L. Consequences of manganese replacement of copper for prion protein function and proteinase resistance. EMBO J. 2000;19:1180–1186
  6. Brown D, Wong B, Haziz F, Clive C, Haswell S, Jones I. Normal prion protein has an activity like that of superoxide dismutase. Biochem J. 1999;344:1–5
  7. Halliwell B, Gutteridge JMO. Free Radicals in Biology and Medicine, 2nd edn. Oxford: Clarendon Press,; 1989;
  8. Forman H, Cadenas E. Oxidative Stress and Signal transduction. New York: Chapman and Hall,. 1997;
  9. Aschner M, Aschner JL. Manganese neurotoxicity; cellular effects and blood brain barrier transport. Neurosci Biobehav Rev. 1991;15:333–340
  10. Barbeau A. Manganese and extra pyramidal disorders. Neurotoxicol. 1984;5:13–36
  11. Martz W. Trace Elements in Human and Animal Nutrition. New York: Academic Press,. 1986;
  12. Mena I. Manganese. In:  Brouser F,  Ford ED editor. Disorders of Mineral Metabolism;. Trace minerals New York Academic Press; 1981;p. 233–270
  13. Cotzias G. Manganese, melanins and the extrapyramidal system. J Neurosurg. 1966;24:170–180
  14. Huselton C, Hill H. Melanin photosensitises UVC DNA damage in pigmented cells. Env Mol Mutagenesis. 1990;16:37–43
  15. Brown D, Qin K, Herms J. The cellular prion protein binds copper in vivo. Nature. 1997;390:684–687
  16. Hornshaw M, McDermott J, Candy J, Lakey J. Copper binding to the N-terminal tandem repeat region of mammalian and avian PrP; Structural studies using synthetic peptides. Biochem Biophys Res. Commun. 1995;214:993–999
  17. Collinge J, Sidle KCL, Meads J, Ironside J, Hill AF. Molecular analysis of prion strain variation and the aetiology of ‘new variant’ CJD. Nature. 1996;383:685–690
  18. Alpers M, Attenborough RD, Alpers M. Kuru. Human Biology in Papua New Quinea. Oxford: Clarendon Press; 1992; p. 312–333
  19. Collinge, J. Proceedings of the National Academy of Science 2000, vol. 97, p, 10248.
  20. Lidiard H, Rae J, Parker A. Identification of Mn oxide minerals in some soils from Devon, UK, and their varying capacity to absorb Co and Cu. Environ Geochem Hlth. 1993;15:93–104
  21. Spraker TR, Miller MW, Williams ES. Spongiform encephalopathy in free ranging Mule deer, White-tailed deer and Rocky Mountain Elk in North Central Colorado. J Wildlife Dis. 1997;33:1–6
  22. Williams ES, Young S. Spongiform encephalopathies in Cervidae. Rev Sci Tech Off Int Epiz. 1992;11:551–567
  23. Barrick KA, Schoettle AW. A comparison of the foliar nutrient status of elfinwood and symmetrically formed tall trees, Colorado Front Range, USA. Can J Bot. 1996;74:1461–1475
  24. Sisler, J. F. Spatial and seasonal patterns and long term variability of the composition of the haze in the USA; an analysis of data from the IMPROVE network. July 1996. ISSN; 0737–5352–32. CIRA, Colorado State University, Fort Collins, CO 80523, USA.
  25. Sisler, J. F. Huffman, D. Spatial and temporal patterns and the chemical composition of the haze in the USA; An analysis of data from the improve network 1988–1991. February 1993. ISSN no 0737–5352–26. CIRA Foothills Campus, Colorado State University, Fort Collins, CO 80523, USA.
  26. Park C. Acid Rain. London: Methuen,; 1987;
  27. Mitrova E. Some new aspects of CJD epidemiology in Slovakia. Eur J Epidemiol. 1991;7:439–449
  28. Mayer V, Orolin D, Mitrova E, Lehotsky T. Transmissible virus dementia. 1. An unusual space and time clustering of CJD and of other organic presenile dementia cases. Acta Virol. 1978;22:146–153
  29. Mitrova F, Bronis M. Clusters of CJD in Slovakia; the first statistically significant temporo-spatial accumulations of rural cases. Eur J Epidemiol. 1991;7:450–456
  30. Mitrova E, Huncaga S, Hocman G. Clusters of CJD in Slovakia 11; The first evidence of scrapie in Czecko-Slovakia. Eur J Epidemiol. 1991;7:457–467
  31. Nosal R, Kapoor A, Shanin R. Cluster of cases of CJD in Ontario. Can Disp Weekly. 1991;Jan 1, Report 17:12
  32. Sigurdarson, S. Epidemiology of scrapie in Iceland and experience with control measures. Bradley, R. ed. Sub Acute Spongiform Encephalopathies, Brussels and Luxembourg, ECSC EEC EAEC, 1991: 233–242.
  33. Palsson, P. A. Rida (scrapie), in Iceland and its epidemiology. Slow transmissible diseases of the nervous system, vol. 1, London, Academic Press, 1979: 357–366.
  34. D’Alessandro M, Petraroli R, Ladogana A, Pocchiari M. High incidence of CJD in rural Calabria, Italy. Lancet. 1998;352:1989–1990
  35. Tanaka, S. Lieben, J. Harrisburg, P. Mn poisoning and exposure in Pennsylvania Arch Environ Health 1969;19: 674–684.
  36. Gianutsos G, Morrow GR, Morris JB. Accumulation of Mn in rat brain following intranasal administration. Fund Appl Toxicol. 1997;37:102–105
  37. Trace minerals: manganese. Roche ‘Vitec’ Information Sheet A1 4/1, May 1987.
  38. Usage of raw materials in Animal feeds in Great Britain 1984–1995 or personal letters – Alex Clothier, MAFF Statistics, 1, 2, Peasholme Green, York
  39. Eley M, Nicholson K. Chemistry and adsorption–desorption properties of Mn oxides deposited in Forehill water treatment plant, Grampian, Scotland. Environ Geochem Health. 1993;15:85–91
  40. Sly JMA. Review of usage of pesticides in Agriculture and horticulture in England and Wales 1975–1979. Report No 23. London: MAFF Publications,. 1981;
  41. Sly JMA. (Agricultural Development and Advisory Service, Hatching Green, Harpenden, Herts.) Review of usage of pesticides in Agriculture and horticulture in the UK; Report No 41. London: MAFF Publications,. 1985;
  42. Thomas MR. Review of usage of pesticides in agriculture and horticulture throughout GB 1984–1994. Pesticide Usage Survey Report 100: London: MAFF Publications,. 1997;
  43. Trace Elements in soils and crops. Technical Bulletin 21. London: MAFF HMSO,. 1971;
  44. Environmental Health Criteria 17: Manganese. IPCS International Programme on Chemical Saftey. Geneva: World Health Organization,. 1986;
  45. Brown D, Schulz-Schaeffer WJ, Schmidt B, Kretzschmar HA. PrP deficient cells show altered response to oxidative stress due to decreased SOD-1 activity. Exper Neurol. 1997;146:104–112
  46. Brown D, Wong B, Jones I. Recombinant PrP exhibits superoxide dismutase activity. J Neurochem. 1999;
  47. Banta RG, Markesbury WR. Elevated Mn levels associated with dementia and extrapyramidal signs. Neurology. 1977;27:213–216
  48. Abdel Naby S, Hassanein M. Neuropsychiatric manifestations of chronic manganese poisoning. J Neurol Neurosurg Psychiat. 1965;28:282–288
  49. Ashizawa R. Ueber einen Sektionsfall von chronischer manganvergiftungen. Jap J Med Sci Trans. sect. V111 Intern Med Pediat Psychiat. 1927;1:173–191
  50. Trendtel F. Zur Frage des Manganismus. Mschr Unfallheilk. 1936;43:69–84
  51. Canavan MM, Cobb S, Drinker CK. Chronic manganese poisoning; report of a case with autopsy. Arch Neurol Psychiat (Chicago). 1934;32:501–513
  52. Gibbons RA, Dixon SN, Hallis K, Russell AM, Sansom BF, Symonds HW. Mn metabolism in cows and goats. Biochim Biophys Acta. 1976;444:1–10
  53. Patel BN, David S. A novel GPI anchored form of ceruloplasmin expressed by astrocytes. J Biol Chem. 1997;272:20185–20190
  54. Kimmerle G, Loeser E. Delayed neurotoxicity of op compounds and Cu concentrations in the serum of hens. Environ Qual Safety. 1974;3:173–179
  55. Carruthers MB, Hobbs GB, Warcen RB. Raised ceruloplasmin levels in subjects taking oral contraceptives. J Clin Pathol. 1966;19:498–500
  56. Neff NH, Barrett RE. Costa E. Selective depletion of caudate nucleus dopamine and serotonin during chronic Mn dioxide administration to squirrel monkeys. Experientia. 1969;25:1140–1141
  57. Mustafa SJ, Chandra SV. levels of 5-hyroxytryptamine, dopamine and norepinephrine in whole brain of rabbits in chronic Mn toxicity. J Neurochem. 1971;18:931–933
  58. Bassant MH, Picard M, Olichon D, Cathala F, Court L. Changes in the serotonergic, noradrenergic and dopaminergic levels in the brain of scrapie-infected rats. Brain Res. 1986;367:360–363
  59. Cross AJ, Kimberlin RH, Crow TJ, Johnson JA, Walker CA. Neurotransmitter metabolites, enzymes and receptors in experimental scrapie. J Neurol Sci. 1985;70:231–241
  60. Brun A, Gottfries CG, Roos BE. Studies of the monoamine metabolism in the CNS in CJD. Acta Neurol Scand. 1971;47:642–645
  61. Nyberg P, Almay BGL, Carlsson A, Masters C, Winblad B. Brain monamine abnormalities in two types of CJD. Acta Neurol Scand. 1982;66:16–24
  62. Goudsmit J, Rohwer RG, Silvergeld EK. Hypersensitivity to central serotonin receptor activation in scrapie infected hamsters and the effect of serotonergic drugs on scrapie symptoms. Brain Res. 1981;220:372–377
  63. Bost, M. Kopp, N. Giraud, P. Copper status and screening for other trace elements in CJD patients; preliminary, results. J Alzheimers Disease, 2000, 2
  64. Mena I, Marin O, Fuenzalida S, Cotzias GC. Chronic manganese poisoning. Neurol. 1967;17:128–136
  65. Rawal ML. Manganese poisoning in Mn mines in India. Ind J Industrial Med. 1968;14:41–51
  66. Greenhouse AH. Mn intoxication in the USA. Trans Am Neurol Ass. 1971;96:248–249
  67. Will RG, Ironside JW, Zeidler M. A new variant of CJD in the UK. Lancet. 1996;347:921–925
  68. De Reuck J, De Coster W, vander Eecken H. CJD: a comparative light-microscopic, histochemical and electron microscopic study. Eur Neurol. 1975;13:154–166
  69. Whatley SA, Powell JF, Politopoulou G, Campbell IC, Brammer MJ, Percy NS. Regulation of intracellular free calcium levels by the cellular prion protein. Mol Neurosci. 1995;6:2333–2337
  70. Kristensson K, Feuerstein E, Taraboulos A, Hyun M, Prusiner S, DeArmond S. Scrapie prions alter receptor-mediated calcium responses in cultured cells. Neurology. 1993;43:2335–2341
  71. Robinson N. CJD: a histochemical study. Brain. 1969;92:581–588
  72. Mackensie A. Intraneuronal enzymic inclusions in the histological diagnosis of scrapie. J Comp Pathol. 1984;94:9–24
  73. Ikuta F, Kumanishi T, Ohashi T. Experimental study on CJD. Adv Neurol Sci. 1974;18:46–61
  74. Narang H, Millar N, Asher D, Gajdusek D. Increased multimeric mitochondrial DNA in the brain of scrapie-infected hamsters. Intervirology. 1991;32:316–324
  75. Gabizon R, Prusiner S. Prion liposomes. Biochem J. 1990;266:1–14
  76. Stahl N, Baldwin MA, Teplow DB. Structural studies of the scrapie prion protein using mass spectrometry and amino acid sequencing. Biochem. 1993;32:1991–2002
  77. Hope J, Baybutt H. The key role of the nerve membrane protein PrP in scrapie-like diseases. Sem Neurosci. 1991;3:165–171
  78. Diez-Ewald M, Weintraub L, Crosby W. Interrelationship of iron and manganese metabolism. Proc Soc Exp Biol Med. 1968;129:448–451
  79. Hancock R, Fritze K. Mn porphyrins in erythrocytes. Bioinorg Chem. 1973;3:77
  80. Pittendrigh C. Circadian oscillations and organisation in nervous system. Schmitt F., Wonder F., eds. The Neurosciences: 3rd Study Program Cambridge, MA: The MIT Press,; 1974; p. 435–537
  81. Caughey B. Scrapie associated PrP accumulation and its prevention; insights from cell culture. Brit Med Bull. 1993;49:860–872
  82. Inouye H, Nguyen JT, Fraser PE, Packard AB, Kirschner DA. Histidine residues underlie congo red binding to A beta analog amyloid. International J Experimental Clin Investigaton. 2000;7:179–188
  83. Caughey W, Raymond L, Horiuchi M, Caughey B. Inhibition of protease resistant PrP formation by porphyrins and phthalocyanines. PNSA. 1998;95(21):12117–12122
  84. Bounias M, Andre JF, Kruk I. Synergistic and molecular interactions between the formamidine amitraz and copper (11) sulfate, used against the mite Varroa jacobsoni O., a parasite of the honeybee Apis mellifera. Biometals. 1993;6:49–53
  85. Brown DP, Schmidt B, Kretzschmar HA. A PrP fragment primes Type 1 astrocytes to proliferation signals from microglia. Neurobiol Dis. 1998;4:410–422
  86. Menaker M. Rhythms, reproduction and photoreception. Biol Reprod. 1971;4:295–308
  87. Lisk R, Kannwischer L. Light: evidence for its direct effect hypothalamic neurones. Science. 1964;146:272–273
  88. Ganong W, Shephard M, Wall J, Van Brunt E, Glegg M. Penetration of light into the brain of mammals. Endocrinology. 1963;72:962–963
  89. Devlin TM. Textbook of Biochemistry with Clinical Correlations, 3rd edn. New York: Wiley-Lisf,; 1992;
  90. Flynn A, Francmann AW, Arneson PD, Oldemever JL. Indications of Cu deficiency in a subpopulation of Alaskan moose. J Nutri. 1977;107:1182–1189
  91. Tobler L, Gaus E, Deboer T. Altered circadian activity rhythms and sleep in mice devoid of PrP. Nature. 1996;380:639–642
  92. Cagampang FR, Whatley S, Powell JF, Mitchel AL, Campbell IG, Cohen W. Circadian regulation of PrP messenger RNA in rat forebrain; a widespread and synchronous rythmn. Neurosi. 1999;91:1201–1204
  93. Morton DJ. Alteration of plasma cation levels in rats kept in constant light. J Pineal Res. 1990;9:95–101
  94. Barnett K, Palmer A. Retinopathy in sheep affected with natural scrapie. Res Vet Sci. 1971;12:383–385
  95. Hogan R, Kingsbury D, Baringer D. Retinal degeneration in experimental CJD. Lab Invest. 1983;49:708–715
  96. Hogan P, Baringer J, Prusiner S. Progressive retinal degeneration in scrapie infected hamsters. Lab Invest. 1981;44:34–42
  97. Fowler M, Robertson N. Observations on Kuru. 111. Pathological features in 5 cases. Aust Ann Med. 1959;8:16–26
  98. Roth A, Keltner J, Ellis W. Virus simulated structures in the optic nerve head in CJD. Am J Opthalmol. 1979;87:827–833
  99. Buyukmihci N, Marsh R, Albert D. Ocular effects of scrapie agent in hamsters; preliminary observations. Invest Ophthalmol. 1977;16:319–324
  100. Buyukmihci N, Rorvik M, Marsh R. Replication of the scrapie agent in ocular neural tissues. Proc Natl Acad Sci USA. 1980;77:1169–1171
  101. Foster J, Fraser H, Bruce M. Retinopathy in Mice with experimental scrapie. Neuropath Appl Neurobiol. 1986;12:185–196
  102. Hogan R. Replication of scrapie prions in hamster eye precedes retinal degeneration. Ophthalmol Res. 1986;18:230–235
  103. Buyukmihci N, Goehring-Harmon F, Marsh R. Neural pathogenesis of experimental scrapie after intraocular inoculation of hamsters. Exp Neurol. 1983;81:396–406
  104. Buyukmihci N, Goehring-Harmon F, Marsh R. Asymmetry of retinal lesions in experimental scrapie after intracerebral inoculation. of hamsters. Exp Neurol. 1985;87:172–176
  105. Tarkkanen A, Haltia M. CJD. Trans Ophthalmol Soc UK. 1980;100:151–154
  106. Ultra violet Radiation; Environmental health Criteria, 14. Geneva: WHO publications, 1979.
  107. Akai J, Ishihara O, Higuchi S. CJD in Japan. Neuroepidemiology. 1989;8:32–37
  108. Detwiler LA. Scrapie. Rev Sci Tech Off Int Epiz. 1992;11:491–537
  109. Agrimi U, Riu G, Cardone F, Pocchiari M, Caramelli M. Epidemic of TSE in sheep and goats in Italy. Lancet. 1999;353:560–561
  110. Kemp D. Global Environmental Issues, 2nd edn. London: Rowtledge,; 1994;
  111. Rinette H, Julicher L, Tijburg L, Aaalt B, Koomen J, Noordhoek J. Decreased defence against free radicals in rat heart during normal rederfusion after hypoxic, ischemic and calcium free perfusion. Life Sci. 1984;35:1281–1288
  112. Dux E, Temesvari P, Joo F. The blood brain barrier in hypoxia. Neurosci. 1984;12:951–958
  113. The Potential Effects of Ozone Depletion in the UK. Dept of Environment HMSO Stationers, London: 1992.
  114. Makhijani A, Gurney K. Mending the Ozone Hole. Cambridge, MA: MIT Press,. 1995;
  115. Ozone in the UK. 3rd Report of the Photochemical Oxidants Review Group. London: HMSO,. 1993;
  116. Ozone: health hazards and precautionary, measures. Health and Saftey Executive. Guidance Note EH 38 (revised) 1996. HSE Books, Sudbury, Suffolk, UK.
  117. Collins S, Law MG, Fletcher A, Boyd A, Caldor J, Masters CJ. Surgical treatment and risk of sporadic CJD; a case control study. Lancet. 1999;353:693–697
  118. Kovanen J, Haltia M. Descriptive epidemiology of CJD in Finland. Acta Neurol Scand. 1988;77:474–480
  119. Masters GL, Harris JO, Gajdusek C, Gibbs CJ, Bernoulli C, Asher DM. CJD: Patterns of worldwide occurrence and the significance of familial and sporadic clustering. Ann Neurol. 1979;5:177–188
  120. CJD surveillance in the UK. 7th Annual Report. National CJD Surveillance Unit, Western General Hospital, Edinburgh EH4 2XU, UK,. 1998;
  121. CJD Surveillance in the UK. 8th Annual Report. National CJD Surveillance Unit, Western General Hospital, Edinburgh, EH4 2XU, UK,. 1999;
  122. Diffey R, Gibson C, Haylock R, McKinlay A. Outdoor UV exposure of children and adolescents. Br J Dermatol. 1996;3:67–82
  123. Diffey B. Analysis of the risk of skin cancer from sunlight and solaria in subjects living in N Europe. Photodermatology. 1987;4:118–126
  124. Elwood J. Melanoma and sun exposure: contrast between intermittent and chronic exposure. World J Surg. 1992;16:157–165
  125. Acheson E. From the chief Medical Officer. Mortality from cutaneous malignant melanoma. Health Trends. 1986;18:73
  126. Lawrence D, Bennet P. Clinical Pharmacology, 5th edn. New York: Churchill Livingstone,; 1980;
  127. Yannuzzi I, Fisher Y, Slakter J, Krueger A. Solar retinopathy. Retina. 1989;9:28–43
  128. MAFF. BSE in Great Britain. A progress report. June 2000. London: MAFF Publications, 2000.
  129. Armstrong B, Kricker A. Cutaneous melanoma. Cancer Surveys. 1994;19:219–240
  130. Rees H. The British Isles – A Regional Geography. London: George Harrap,. 1968;
  131. Mackie R, Hunter J. Cutaneous malignant melanoma in Scotland 1979–1989. Lancet. 1992;339:971–975
  132. Purdey M. High dose exposure to systemic phosmet insecticide modifies the phosphatidylinositol anchor on the prion protein; the origins of new variant transmissible spongiform encephalopathies. Med Hypotheses. 1998;50:91–111
  133. Purdey M. Are organo-phosphate pesticides involved in the causation of BSE? Hypothesis based upon a literature review and limited trials on BSE cattle. J Nutri Med. 1994;4:43–82
  134. Bounias, M. Purdey, M. An epidemiological evaluation of a possible link between BSE and pesticide treatments in France. 2001, under peer review
  135. Goldstein A, Aronow L, Kalman SM, 2nd edn. Wiley International Edition. New York: John Wiley,; 1974;
  136. Pattison IH, Jebbett JN. Spongiform encephalopathy induced in rats and guinea pigs by cuprizone. Exp Mol Pathol. 1969;10:274–287
  137. Yang ZP, Morrow J, Aiping W, Roberts I, Dettbarn WD. Diispropylphosphorofluoridate-induced muscle hyperactivity associated with enhanced lipid peroxidation in vivo. Biochem Pharmacol. 1996;52:357–361
  138. Bagchi D, Bagchi M, Hassoun E, Stohs S. In vitro and in vivo generation of reactive oxygen species, DNA damage and lactate dehydrogenase leakage by selected pesticides. Toxicology. 1995;104:129–140
  139. Myshkin V, Vakarina A, Bashkatov S, Sofronov G, Enikeev D. Postintoxication hypothermia and free radical lipid oxidation in the brain and heart of rats poisoned with OP cholinesterase inhibitors. Bull Exper Biol Med. 1992;113:493–494
  140. Hai D, Varga S, Matkovics B. OP effects on antioxidant system of carp and catfish. Comp Biochem Physiol. 1997;117C:83–85
  141. Matkovics P, Szabo L, Mindszenty L, Ivan J. The effects of OP pesticides on some liver enzymes and lipid peroxidation. Gen Pharmacol. 1980;11:353–355
  142. Chopra A, Ahuja S, Gupta P, Nagpal S. Histopathological and lipid changes in various organs of chicks caused by acute and chronic toxicity of metasystox-R and Lebaycid. Zbl Vet Med A. 1979;26:822–834
  143. Gordon I, Abdulla E, Campbell I, Whatley S. Phosmet induces up-regulation of the surface expression of prion protein. Neuroreport. 1998;9:1391–1395
  144. Karlin S, Zhan-Yang Z, Karlin KD. The extended environment of mononuclear metal centres in protein structures. Proc Natl Acad Sci USA. 1997;Dec 94:14225–14230

PII: S0306-9877(01)91305-2

doi: 10.1054/mehy.2001.1305

Medical Hypotheses
Volume 57, Issue 1 , Pages 29-45 , July 2001

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