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Environmental Copper and Manganese in the Pathophysiology of Neurologic Diseases (Alzheimer's Disease and Manganism)

2005; Wiley; Volume: 33; Issue: 1 Linguagem: Inglês

10.1002/aheh.200400556

1521-401X

Hermann H. Dieter, Thomas A. Bayer, Gerd Multhaup,

Heavy Metal Exposure and Toxicity

Acta hydrochimica et hydrobiologicaVolume 33, Issue 1 p. 72-78 Review Environmental Copper and Manganese in the Pathophysiology of Neurologic Diseases (Alzheimer's Disease and Manganism)† Hermann H. Dieter, Corresponding Author Hermann H. Dieter [email protected] Umweltbundesamt, Berlin, FG Toxikologie des Trink- und Badebeckenwassers, Postfach 330022, 14191 Berlin, GermanyUmweltbundesamt, Berlin, FG Toxikologie des Trink- und Badebeckenwassers, Postfach 330022, 14191 Berlin, GermanySearch for more papers by this authorThomas A. Bayer, Thomas A. Bayer Universität des Saarlandes, Klinik für Psychiatrie, Abteilung für Neurobiologie, 66421 Homburg, GermanySearch for more papers by this authorGerd Multhaup, Gerd Multhaup Freie Universität Berlin, Institut für Chemie/Biochemie, Thielallee 63, 14195 Berlin, GermanySearch for more papers by this author Hermann H. Dieter, Corresponding Author Hermann H. Dieter [email protected] Umweltbundesamt, Berlin, FG Toxikologie des Trink- und Badebeckenwassers, Postfach 330022, 14191 Berlin, GermanyUmweltbundesamt, Berlin, FG Toxikologie des Trink- und Badebeckenwassers, Postfach 330022, 14191 Berlin, GermanySearch for more papers by this authorThomas A. Bayer, Thomas A. Bayer Universität des Saarlandes, Klinik für Psychiatrie, Abteilung für Neurobiologie, 66421 Homburg, GermanySearch for more papers by this authorGerd Multhaup, Gerd Multhaup Freie Universität Berlin, Institut für Chemie/Biochemie, Thielallee 63, 14195 Berlin, GermanySearch for more papers by this author First published: 11 April 2005 https://doi.org/10.1002/aheh.200400556Citations: 53 † Paper presented in part at the Late Summer Workshop “Monitoring Toxic Effects in Aquatic Systems”, Schloss Maurach, Lake Constance, September 2003 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstracten Alzheimer's disease (AD) is the most common form of dementia. Populations migrating from developing to industrialized countries seem to elicit a higher incidence and prevalence rate of AD, suggesting lifestyle and environmental factors to have a role in the pathophysiology of AD. One of its major neuropathological hallmarks is the deposition of Aβ peptides as amyloid plaques in the brain of AD patients. Aβ is proteolytically cleaved out of the larger amyloid precursor protein (APP). Cu and Mn are often found in drinking water and may have a neurotoxic potential. APP is involved in Cu homeostasis in mouse and man. In vitro observations and in vivo data obtained from APP mouse models provide strong evidence that APP overexpression enables intracellular Cu to be transported out of the cell. Disturbed metal-ion homeostasis with elevated serum Cu levels occurs in Alzheimer and Down's patients and lowered levels in post-mortem AD brain. We observed that bioavailable Cu has specific beneficial effects in an Alzheimer's disease mouse model. This should be regarded as a proof-of-concept for a prophylactic approach to overcome the observed CNS Cu deficiency in the brain of Alzheimer's disease patients. Manganism is a disorder with symptoms similar to that of Parkinson's disease. The precise mechanism how manganese can damage the nervous system is unknown. There is some evidence that iron and manganese may utilize similar transport systems. Epidemi ologic data strongly suggests that manganese enters the body primarily via inhalation and through the ingestion of manganese in drinking water. Abstractde Kupfer und Mangan aus der Umwelt und die Pathophysiologie neurologischer Erkrankungen (Alzheimer-Krankheit und Manganismus) Die Alzheimer-Krankheit (AD) ist die häufigste Form der Altersdemenz. In Bevölkerungsgruppen, die aus Entwicklungs- in industrialisierte Länder übersiedeln, steigen parallel dazu absolute und relative Häufigkeit der AD. Lebensweise und Umwelt scheinen demnach die Pathophysiologie der AD zu beeinflussen. Eines ihrer wichtigsten Merkmale ist die Ablagerung von Aβ-Peptiden in Form von Amyloidplatten im Gehirn. Das Aβ-Peptid entsteht proteolytisch aus einem größeren Vorläufermolekül, dem Amyloid-precursor protein (APP). Cu und Mn kommen oft im Trinkwasser vor und könnten beide ein neurotoxisches Potential besitzen. APP ist in den Stoffwechsel von Cu in Maus und Mensch eingebunden. Beobachtungen in vitro und In-vivo-Daten aus Mausmodellen belegen zweifelsfrei, dass die Überexpression von APP dem Cu das Verlassen der Zelle ermöglicht. In Patienten mit AD oder dem Down-Syndrom sind infolge Störung der Metall-Homöostase die Cu-Werte im Serum erhöht und im Gehirn verstorbener AD-Patienten erniedrigt. Wir selbst beobachteten, dass bioverfügbares Cu im Mausmodell Entstehung und Verlauf der AD mildert. Dies ist ein vielversprechender Ausgangspunkt für die Suche nach Möglichkeiten, die Cu-Verarmung bestimmter Gehirnbereiche von AD-Patienten prophylaktisch zu unterlaufen. Der genaue Mechanismus, nach dem Mn das Gehirn schädigen kann, ist unbekannt. Es erreicht den Körper vermutlich unter Nutzung der Transportsysteme für Fe vor allem per Inhalation und auf dem Trinkwasserpfad. Die Symptomatik des Manganismus ähnelt derjenigen des Parkinsonismus. REFERENCES 1 Bayer, T. A., Cappai, R., Masters, C. L., Beyreuther, K., Multhaup, G., It all sticks together – the APP-related family of proteins and Alzheimer′s disease. Mol. Psychiatry, 4, 524– 528, (1999). 2 Hesse, L., Beher, D., Masters, C. L., Multhaup, G., The beta A4 amyloid precursor protein binding to copper. Febs Lett., 349, 109– 116, (1994). 3 Atwood, C. S., Scarpa, R. C., Huang, X., Moir, R. D., Jones, W. D., Fairlie, D. P., Tanzi, R. E., Bush, A. I., Characterization of copper interactions with Alzheimer amyloid beta peptides identification of an attomolar-affinity copper binding site on amyloid beta1-42. J. Neurochem., 75, 1219– 1233, (2000). 4 Multhaup, G., Schlicksupp, A., Hesse, L., Beher, D., Ruppert, T., Mastes, C. L., Beyreuther, K., The amyloid precursor protein of Alzheimer′s disease in the reduction of copper(II) to copper(I). Science, 271, 1406– 1409, (1996). 5 Bush, A. I., The metallobiology of Alzheimer′s disease. Trends Neurosci., 26, 207– 214, (2003). 6 Multhaup, G., Scheuermann, S., Schlicksupp, A., Simons, A., Strauss, M., Kemmling, A., Oehler, C., Cappai, R., Pipkorn, R., Bayer, T. A., Possible mechanisms of APP-mediated oxidative stress in Alzheimer′s disease(1,2). Free Radic. Biol. Med., 33, 45– 51, (2002). 7 White, A. R., Reyes, R., Mercer, J. F., Camakaris, J., Zheng, H., Bush, A. I., Multhaup, G., Beyreuther, K., Masters, C. L., Cappai, R., Copper levels are increased in the cerebral cortex and liver of APP and APLP2 knockout mice. Brain Res., 842, 439– 444, (1999). 8 Maynard, C. J., Cappai, R., Volitakis, I., Cherny, R. A., White, A. R., Beyreuther, K., Masters, C. L., Bush, A. I., Li, Q. X., Overexpression of Alzheimer′s disease amyloid-beta opposes the age-dependent elevations of brain copper and iron. J. Biol. Chem., 277, 44670– 44676, (2002). 9 Borchardt, T., Camakaris, J., Cappai, R., Masters, C. L., Beyreuther, K., Multhaup, G., Copper inhibits beta-amyloid production and stimulates the non-amyloidogenic pathway of amyloid-precursor-protein secretion. Biochem. J., 344, 461– 467, (1999). 10 Phinney, A. L., Drisaldi, B., Lugowski, S., Schmidt, S. D., Coronado, V., Liang, Y., Horne, P., Yang, J., Sekoulidis, J., Coomaraswamy, J., In vivo reduction of amyloid Aá by a mutant copper transporter. PNAS, 100, 14193– 14198, (2003). 11 Bayer, T. A., Schäfer, S., Simons, A., Kemmling, A., Kamer, T., Tepest, R., Eckert, A., Schüssel, K., Eikenberg, O., Sturchler-Pierrat, C., Dietary Cu stabilizes brain SOD-1 activity and reduces amyloid Aá production in APP23 transgenic mice. PNAS, 100, 14187– 14192, (2003). 12 Cherny, R. A., Atwood, C. S., Xilinas, M. E., Gray, D. N., Jones, W. D., MacLean, C. A., Barnham, K. J., Volitakis, I., Fraser, F. W., Kim, Y., Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer′s disease transgenic mice. Neuron, 30, 665– 676, (2001). 13 Carlton, W. W., Spongiform encephalopathy induced in rats and guinea pigs by cuprizone. Exp. Mol. Pathol., 10, 274– 287, (1969). 14 Sparks, D. L., Schreurs, B. G., Trace amounts of copper in water induce beta-amyloid plaques and learning deficits in a rabbit model of Alzheimer′s disease. PNAS, 100, 11065– 11069, (2003). 15 Bush, A. I., Masters, C. L., Tanzi, R., Copper, á-amyloid, and Alzheimer′s disease tapping a sensitive connection. PNAS, 100, 11193– 11194, (2003). 16 Squitti, R., Lupoi, D., Pasqualetti, P., Dal Forno, G., Vernieri, F., Chiovenda, P., Rossi, L., Cortesi, M., Cassetta, E., Rossini, P. M., Elevation of serum copper levels in Alzheimer′s disease. Neurology, 59, 1153– 1161, (2002). 17 Carlson, G. A., Borchelt, D. R., Dake, A., Turner, S., Danielson, V., Coffin, J. D., Eckman, C., Meiners, J., Nilsen, S. P., Younkin, S. G., Hsiao, K. K., Genetic modification of the phenotypes produced by amyloid precursor protein overexpression in transgenic mice. Hum. Mol. Genet., 6, 1951– 1959, (1997). 18 Iadecola, C., Zhang, F., Niwa, K., Eckman, C., Turner, S. K., Fischer, E., Younkin, S., Borchelt, D. R., Hsiao, K. K., Carlson, G., SOD-1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein. Nat. Neurosci., 2, 157– 61, (1999). 19 McLoughlin, D. M., Standen, C. L., Lau, K. F., Ackerley, S., Bartnikas, T. P., Gitlin, J. D., Miller, C. C., The neuronal adaptor protein X11alpha interacts with the copper chaperone for SOD1 and regulates SOD1 activity. J. Biol. Chem., 276, 9303– 9307, (2001). 20 Bartnikas, T. B., Gitlin, J. D., Mechanisms of biosynthesis of mammalian copper/zinc superoxide dismutase. J. Biol. Chem., 278, 33602– 33608, (2003). 21 Canavan, M. M., Cobb, S., Drinker, C., Chronic manganese poisoning. Arch. Neurol. Psychiatry, 32, 501– 512, (1934). 22 Cook, D. G., Fahn, S., Brait, K. A., Chronic manganese intoxication. Arch. Neurol., 30, 59– 64, (1974). 23 Roels, H. A., Ortega Eslava, M. I., Ceulemans, E., Robert, A., Lison, D., Prospective study on the reversibility of neurobehavioral effects in workers exposed to manganese dioxide. Neurotoxicology, 20, 255– 271, (1999). 24 Roels, H. A., Ghyselen, P., Buchet, J. P., Ceulemans, E., Lauwerys, R. R., Assessment of the permissible exposure level to manganese in workers exposed to manganese dioxide dust. Brit. J. Industr. Med., 49, 25– 34, (1992). 25 Mergler, D., Huel, G., Bowler, R., Iregren, A., Bélanger, S., Baldwin, M., Tardif, R., Smargiassi, A., Martin, L., Nervous system dysfunction among workers with long-term exposure to manganese. Environ. Res., 64, 151– 180, (1994). 26 Eriksson, H., Gillberg, P.-G., Aquilonius, S.-M., Hedström, K.-G., Heilbronn, E., Receptor alternations in manganese intoxicated monkeys. Arch. Toxicol., 66, 359– 364, (1992). 27 Gavin, C. E., Gunter, K. K., Gunter, T. E., Mn2+ sequestration by mitochondria and inhibition of oxidative phosphorylation. Toxicol. Appl. Pharmacol., 115, 1– 5, (1992). 28 Komura, J., Sakamoto, M., Effects of manganese forms on biogenic amines in the brain and behavioral alterations in the mouse Long-term oral administration of several manganese compounds. Environ. Res., 57, 34– 44, (1992). 29 Chen, J.-Y., Tsao, G. C., Zhao, Q., Zheng, W., Differential cytotoxicity of Mn(II) and Mn(III) Special reference to mitochondrial [Fe-S] containing enzymes. Toxicol. Appl. Pharmacol., 175, 160– 168, (2001). 30 Manganese Conference: Summary reports on sessions I–VIII. NeuroToxicology 19, 452–489 (1998). Session II: Toxicokinetics and bioavailability of manganese, 475–478; Session III: Manganese and human health – Part I, 479–480; Session VI: Mechanisms of toxic action – Animal models, 483–485; Session VII: Related recent occupational studies of manganese, 486–487. 31 Korc, M.: Manganese. In: (Ed.): Current Tropics in Nutrition and Disease, Vol. 18: Essential and Toxic Trace Elements in Human Health and Disease. Alan R. Liss Inc., New York, 1988, pp. 253– 273. 32 Brown, D. R., Hafiz, F., Glassmith, L. L., Wong, B.-S., Jones, I. M., Clive, C., Haswell, S. J., Consequences of manganese replacement of copper for prion protein function and proteinase resistance. The EMBO Journal, 19, 1180– 1186, (2000). 33 Florence, T. M., Stauber, J. L., Manganese katalysis of dopamine oxidation. Sci. Total Environ., 78, 233– 240, (1989). 34 Iwami, O., Watanabe, T., Moon, C. S., Nakatsuka, H., Ikeda, M.:, Motor neuron disease on the Kii Peninsula of JapanExcess manganese intake from food coupled with low magnesium in drinking water as a risk factor. Sci. Total Environ., 149, 121– 135, (1994). 35 Yoshida, S., Yase, Y., Iwata, S., Mizumoto, Y., Chen, K.-M., Gajdusek, D. C., Comparative trace-elemental study on amyotrophic lateral sclerosis (ALS) and Parkinsonism-dementia (PD) in the Kii Peninsula of Japan and Guam. Wakayama Med. Rep., 30, 41– 53, (1998). 36 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. Medical Hypotheses, 54, 278– 306, (2000). 37 Gianutsos, G., Morrow, G. R., Morris, J. B., Accumulations of manganese in rat brain, following intranasal administration. Fundam. Appl. Toxicol., 37, 102– 105, (1997). 38 Roels, H., Meiers, R., Delos, M., Ortega, I., Lauwerys, R., Buchet, J. P., Lison, D., Influence of the route of administration and the chemical form (MnCl2, MnO2) on the absorption and cerebral distribution of manganese in rats. Arch. Toxicol., 71, 223– 230, (1997). 39 Brenneman, K. A., Wong, B. A., Buccellato, M. A., Costa, E. R., Gross, E. A., Dorman, D. C., Direct olfactory transport of inhaled manganese (54MnCl2) to the rat brain Toxi cokinetic investigations in a unilateral nasal occlusion model. Toxicol. Appl. Pharmacol., 169, 238– 248, (2000). 40 Tjälve, H., Henriksson, J., Tallkvist, J., Larsson, B. S., Lindquist, N. G., Uptake of manganese and cadmium from the nasal mucosa into the central nervous system via olfactory pathways in rats. Pharmacol. Toxicol., 79, 347– 356, (1996). 41 Vitarella, D., Wong, B. A., Moss, O. R., Dorman, D. C., Pharmacokinetics of inhaled manganese phosphate in male sprague-dawley rats following subacute (14-day) exposure. Toxicol. Appl. Pharmacol., 163, 279– 285, (2000). 42 Bench, G., Carlsen, T. M., Grant, P. G., Wollett, J. S. Jr., Martinelli, R. E., Lewis, J. L., Divine, K. K., Olfactory bulb uptake and determination of biotransfer factors in the California ground squirrel (Spermophilus beecheyi) exposed to manganese and cadmium in environmental habitats. Environ. Sci. Technol., 35, 270– 277, (2001). 43 Dorman, D. C., Brenneman, K. A., McElveen, A., Lynch, S. E., Roberts, K., Wong, B., Olfactory transport a direct route of delivery of inhaled manganese phosphate to the rat brain. J. Toxicol. Eviron. Health, 65, 1493– 1511, (2002). 44 Henriksson, J., Tjälve, H., Manganese taken up into the CNS via the olfactory pathway in rats affects astrocytes. Toxicol. Sci., 55, 392– 398, (2000). 45 Rao, D. B., Wong, B. A., McManus, B. E., McElveen, A. M., James, A. R., Dorman, C., Inhaled iron, unlike manganese, is not transported to the rat brain via the olfactory pathway. Toxicol. Appl. Pharmacol., 193, 116– 126, (2003). 46 Ingersoll, R. T., Montgomery, E. B.Jr., Aposhian, H. V., Central nervous system toxicity of manganese. I. Inhibition of spontaneous motor activity in rats after intrathecal administration of manganese chloride. Fundam. Appl. Toxi col., 27, 106– 113, (1995). 47 Zheng, W., Perry, D. F., Nelson, D. L., Aposhian, H. V., Choroid plexus protects cerebrospinal fluid against toxic metals. FASEB J., 5, 2188– 2193, (1991). 48 Hauser, R. A., Zesiewicz, T. A., Rosemurgy, A. S., Martinez, C., Olanow, C. W., Manganese intoxication and chronic liver failure. Ann. Neurol., 36, 871– 875, (1994). 49 Pomier-Layrargues, G., Spahr, L., Butterworth, R. F., Increased manganese concentrations in pallidum of cirrhotic patients. Lancet, 345, 735, (1995). 50 Wang, J. D., Chuang, C. C., Hwang, Y. H., Chiang, J. R., Lin, J. M., Chen, J. S., Manganese induced Parkinsonism an outbreak due to unrepaired ventilation control system in a ferromanganese smelter. Brit. J. Industr. Med., 46, 856– 859, (1989). 51 Loranger, S., Zayed, J., Environmental and occupational exposure to manganese a multimedia assessment. Int. Arch. Occup. Environ. Health, 67, 101– 110, (1995). 52 Kondakis, X. G., Makris, M., Leotsinidis, M., Prinou, M., Papapetropoulos, T., Possible health effects of high manganese concentration in drinking water. Arch. Environ. Health, 44, 175– 178, (1989). 53 Peng, H., Dehua, L., Gongqiao, Z., Effects of high-level sewage irrigation on children′s neurobehaviour. Chin. J. Prev. Med., 28, 216– 218, (1995). 54 Gongqiao, Z., Dehua, L., Peng, H., Effects of manganese on learning abilities in school children. Chin. J. Prev. Med., 29, 156– 158, (1995). 55 Woolf, A., Wright, R., Amarasiriwardena, C., Bellinger, D., A child with chronic manganese exposure from drinking water. Environ. Health Perspect., 110, 1– 4, (2002). 56 Korf, G. P.: Langzeitgenuss von brunnengefördertem Trinkwasser unterschiedlichen Mangangehalts und neuro logische Störungen. Eine umweltmedizinische Quer schnitt studie. (Neurologic disturbances and the long-term ingestion of drinking water from private wells with different Mn levels. A cross-sectional environmental health study) Dissertation, Universität Lübeck, 1994. Citing Literature Volume33, Issue1April 2005Pages 72-78 ReferencesRelatedInformation