Metals and neuroscience

Current Opinion in Chemical Biology

Volumn 4, Issue 2, 2000, Pages 184-191

  Bush, Ashley I ^a  

^a Genet Aging U Massachusetts G   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COPPER; COPPER ZINC SUPEROXIDE DISMUTASE; IRON; METAL ION;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; CATARACT; DISORDERS OF MITOCHONDRIAL FUNCTIONS; HUMAN; NEUROLOGIC DISEASE; OXIDATION REDUCTION REACTION; PARKINSON DISEASE; PRION DISEASE; PROTEIN INTERACTION; REVIEW;

EID: 0034035616     PISSN: 13675931     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1367-5931(99)00073-3     Document Type: Review

References (52)

1. Lovell M.A., Robertson J.D., Teesdale W.J., Campbell J.L., Markesbery W.R. Copper, iron and zinc in Alzheimer's disease senile plaques. J Neurol Sci. 158:1998;47-52. A consensus has emerged in the literature that Cu, Zn and Fe are elevated in the AD-affected neocortex. Lovell et al., have studied AD and age-matched control brain specimens using the microparticle-induced X-ray emission technique to pin-point elegantly the microanatomical distribution of these elevated metal ions, showing that they are particularly enriched in Aβ amyloid deposits.
2. Frederickson C.J. Neurobiology of zinc and zinc-containing neurons. Int Rev Neurobiol. 31:1989;145-328.
3. Maret W., Jacob C., Vallee B.L., Fischer E.H. Inhibitory sites in enzymes: zinc removal and reactivation by thionein. Proc Natl Acad Sci USA. 96:1999;1936-1940. This paper shows for the first time the breadth of enzyme activities that are inhibited by nanomolar elevations in zinc concentration. These activities include caspase-3, a protein that mediates apoptosis.
4. Jacob C., Maret W., Vallee B.L. Control of zinc transfer between thionein, metallothionein, and zinc proteins. Proc Natl Acad Sci USA. 95:1998;3489-3494. The Vallee group have shown that metallothionein is not just a passive dump for heavy metals but an important buffering system that is regulated by the redox and energy environments of the cell.
5. •].
6. •].
7. Cole T.B., Wenzel H.J., Kafer K.E., Schwartzkroin P.A., Palmiter R.D. Elimination of zinc from synaptic vesicles in the intact mouse brain by disruption of the ZnT3 gene. Proc Natl Acad Sci USA. 96:1999;1716-1721. The Palmiter group are elaborating the functional aspects of the various zinc transporters they have cloned. It is interesting that the knockouts are viable with a mild phenotype.
8. Rae T.D., Schmidt P.J., Pufahl R.A., Culotta V.C., O'Halloran T.V. Undetectable intracellular free copper: the requirement of a copper chaperone for superoxide dismutase. Science. 284:1999;805-808. One of the most misunderstood and misquoted papers in this field this year. The 'freeing' of metal ions is not the only way that metal ions can bind to proteins. One has to differentiate the concept of bound exchangeable metals from irreversibly bound metals. The O'Halloran group are not saying that because there is no free copper in the cell, copper cannot exchange between proteins, or that there is no copper at all in the cell. They are saying that the copper in the cell is largely bound, but a copper chaperone (CCS) facilitates the exchange of copper from the bound exchangeable pool onto SOD1.
9. Lamb A.L., Wernimont A.K., Pufahl R.A., Culotta V.C., O'Halloran T.V., Rosenzweig A.C. Crystal structure of the copper chaperone for superoxide dismutase. Nat Struct Biol. 6: 1999;24-729. Nature has gone to a lot of trouble to set up a system where the binding of copper to SOD1 is preserved.
10. Atwood C.S., Huang X., Moir R.D., Tanzi R.E., Bush A.I. Role of free radicals and metal ions in the pathogenesis of Alzheimer's disease. Met Ions Biol Syst. 36:1999;309-364.
11. Hartter D.E., Barnea A. Brain tissue accumulates 67copper by two ligand-dependent saturable processes. J Biol Chem. 263:1988;799-805.
12. Atwood C.S., Moir R.D., Huang X., Bacarra N.M.E., Scarpa R.C., Romano D.M., Hartshorn M.A., Tanzi R.E., Bush A.I. Dramatic aggregation of Alzheimer Aβ by Cu(II) is induced by conditions representing physiological acidosis. J Biol Chem. 273:1998;12817-12826. Mildly acidic conditions abolish zinc binding to Aβ and to most proteins like Aβ where histidine mediates copper and zinc-ion coordination. Such conditions dramatically increase Cu binding to Aβ and promote its precipitation, however, perhaps explaining Cu enrichment in Aβ plaque pathology.
13. Huang X., Atwood C.S., Hartshorn M.A., Multhaup G., Goldstein L.E., Scarpa R.C., Cuajungco M.P., Gray D.N., Lim J., Moir R.D.et al. The Aβ peptide of Alzheimer's disease directly produces hydrogen peroxide through metal ion reduction. Biochemistry. 38:1999;7609-7616. Aβ, which accumulates in the brain in AD, produces hydrogen peroxide in a catalytic manner, using oxygen as a substrate. Because oxidation is likely to mediate neurodegeneration in AD, Aβ-mediated hydrogen peroxide production is likely to be a major source of the problem, especially because hydrogen peroxide is freely permeable across cell boundaries.
14. 2), making this molecule a very powerful reducing agent.
15. Kong J., Xu Z. Massive mitochondrial degeneration in motor neurons triggers the onset of amyotrophic lateral sclerosis in mice expressing a mutant SOD1. J Neurosci. 18:1998;3241-3250.
16. Pasinelli P., Borchelt D.R., Houseweart M.K., Cleveland D.W., Brown R.H. Jr. Caspase-1 is activated in neural cells and tissue with amyotrophic lateral sclerosis-associated mutations in copper-zinc superoxide dismutase. Proc Natl Acad Sci USA. 95:1998;15763-15768.
17. c. This paper shows that normal SOD1 cannot overcome the pathogenic problem caused by mutant SOD, indicating that the mutation does not cause a loss of function.
18. Bielski B.H.J., Cabelli D.E., Arudi R.L., Ross A.B. Reactivity of HO2/O2- radicals in aqueous solution. J Phys Chem Ref Data. 14:1985;1041-1100.
19. ••].
20. Lyons T.J., Liu H., Goto J.J., Nersissian A., Roe J.A., Graden J.A., Cafe C., Ellerby L.M., Bredesen D.E., Gralla E.B., Valentine J.S. Mutations in copper-zinc superoxide dismutase that cause amyotrophic lateral sclerosis alter the zinc binding site and the redox behavior of the protein. Proc Natl Acad Sci USA. 93:1996;12240-12244.
21. Crow J.P., Sampson J.B., Zhuang Y., Thompson J.A., Beckman J.S. Decreased zinc affinity of amyotrophic lateral sclerosis-associated superoxide dismutase mutants leads to enhanced catalysis of tyrosine nitration by peroxynitrite. J Neurochem. 69:1997;1936-1944.
22. Nagano S., Ogawa Y., Yanagihara T., Sakoda S. Benefit of a combined treatment with trientine and ascorbate in familial amyotrophic lateral sclerosis model mice. Neurosci Lett. 265:1999;159-162.
23. Calhoun M.E., Wiederhold K.H., Abramowski D., Phinney A.L., Probst A., Sturchler-Pierrat C., Staufenbiel M., Sommer B., Jucker M. Neuron loss in APP transgenic mice. Nature. 395:1998;755-756.
24. Smith M.A., Hirai K., Hsiao K., Pappolla M.A., Harris P., Siedlak S., Tabaton M., Perry G. Amyloid-beta deposition in Alzheimer transgenic mice is associated with oxidative stress. J Neurochem. 70:1998;2212-2215. Aβ accumulation alone is associated with brain oxidation.
25. Moir R.D., Atwood C.S., Romano D.M., Laurans M.H., Huang X., Bush A.I., Smith J.D., Tanzi R.E. Differential effects of apolipoprotein E isoforms on metal-induced aggregation of A-beta using physiological concentrations. Biochemistry. 38:1999;4595-4603.
26. •].
27. •].
28. Gonzalez C., Martin T., Cacho J., Brenas M.T., Arroyo T., Garcia-Berrocal B., Navajo J.A., Gonzalez-Buitrago J.M. Serum zinc, copper, insulin and lipids in Alzheimer's disease epsilon 4 apolipoprotein E allele carriers. Eur J Clin Invest. 29:1999;637-642. Zn and Cu elevation in the AD reflects a systemic problem.
29. Cherny R.A., Legg J.T., McLean C.A., Fairlie D., Huang X., Atwood C.S., Beyreuther K., Tanzi R.E., Masters C.L., Bush A.I. Aqueous dissolution of Alzheimer's disease Aβ amyloid deposits by biometal depletion. J Biol Chem. 274:1999;23223-23228. Here we show that Aβ deposition in the brain in AD is not caused exclusively by hydrophobic forces. Chelators of zinc and copper were used to increase the solubilization of Aβ deposits from post-mortem brain specimens. This may be the basis of a future pharmacotherapy.
30. Atwood C.S., Huang X., Moir R.D., Scarpa R.C., Bacarra N.M.E., Hartshorn M.A., Goldstein L.E., Romano D.M., Tanzi R.E., Bush A.I. Copper-mediated aggregation and polymerization of Aβ Soc Neurosci Abstr. 23:1997;1883.
31. Bush A.I., Pettingell W.H. Jr., Paradis M.D., Tanzi R.E. Modulation of Aβ adhesiveness and secretase site cleavage by zinc. J Biol Chem. 269:1994;12152-12158.
32. 2+. This enabled very accurate measurement of metal binding in the very high affinity range.
33. Frausto da Silva, J.J.R., Williams, R.J.P.: The Biological Chemistry of the Elements Oxford: Clarendon Press; 1991:388-399.
34. Bush A.I., Lynch T., Cherny R.C., Atwood C.S., Goldstein L.E., Moir R.D., Li Q.-X., Cabelli D.E., Multhaup G., Masters C.L.et al. Alzheimer Aβ functions as superoxide antioxidant in vitro and in vivo. Soc Neurosci Abstr. 25:1999;14.
35. c, the cuproprotein that becomes modified, toxic and infectious in TSEs, functions as an SOD. The biochemistry and cell-culture studies in this paper are superb. I know that this paper struggled to be published because reviewers found it hard to accept that such a pathogenic protein could be an SOD-like antioxidant. Thankfully, the editors at Biochemistry Journal saw past this chauvinism.
36. c supports the likelihood the binding serves an important physiological purpose.
37. Brown D.R., Schmidt B., Kretzschmar H.A. Effects of copper on survival of prion protein knockout neurons and glia. J Neurochem. 70:1998;1686-1693.
38. Multhaup G., Schlicksupp A., Hesse L., Beher D., Ruppert T., Masters C.L., Beyreuther K. The amyloid precursor protein of Alzheimer's disease in the reduction of copper(II) to copper(I). Science. 271:1996;1406-1409.
39. Bush A.I., Multhaup G., Moir R.D., Williamson T.G., Small D.H., Rumble B., Pollwein P., Beyreuther K., Masters C.L. A novel zinc(II) binding site modulates the function of the βA4 amyloid protein precursor of Alzheimer's disease. J Biol Chem. 268:1993;16109-16112.
40. c in modulating the distribution of cellular copper. Both APP and APLP2 have homologous copper-binding domains in their amino termini. Loss of the function of these proteins in knockout animals leads to the accumulation of copper both in the brain and liver.
41. White A.R., Multhaup G., Maher F., Bellingham S., Camakaris J., Zheng H., Bush A.I., Beyreuther K., Masters C.L., Cappai R. The Alzheimer's disease amyloid precursor protein modulates copper-induced toxicity and oxidative stress in primary neuronal cultures. J Neurosci. 19:1999;9170-9179.
42. 2+ with PrP in mediating the toxic aspects of the peptide resembles our recent proposal that Cu interaction also mediates the toxicity of Aβ, the amyloidogenic peptide of AD.
43. ••].
44. Bush A.I., Tanzi R.E., Multhaup G., Hartshorn M., Saunders A.J., Atwood C.S., Huang X. PrP and Aβ share a common mechanism of metal-dependent reactive oxygen species production. Soc Neurosci Abstr. 24:1998;508.
45. Hood B.D., Garner B., Truscott R.J. Human lens coloration and aging. Evidence for crystallin modification by the major ultraviolet filter, 3-hydroxy-kynurenine o-beta-D-glucoside. J Biol Chem. 274:1999;32547-32550.
46. Cekic O. Effect of cigarette smoking on copper, lead, and cadmium accumulation in human lens. Br J Ophthalmol. 82:1998;186-188.
47. Goldstein, L.E., Hartshorn, M., Leopold, M.C., Huang, X., Atwood, C.S., Saunders, A.J., Lim, J., Faget, K., Scarpa, R.C., Chylack, L.T. et al.: 3-Hydroxykynurenine and 3-hydroxyanthranilic acid generate hydrogen peroxide and promote α-crystallin crosslinking by metal ion reduction. Biochemistry 2000, in press.
48. Jellinger K.A. The role of iron in neurodegeneration. prospects for pharmacotherapy of Parkinson's disease Drugs Aging. 14:1999;115-140.
49. Paik S.R., Shin H.J., Lee J.H., Chang C.S., Kim J. Copper(II)-induced self-oligomerization of alpha-synuclein. Biochem J. 340:1999;821-828.
50. Radisky D.C., Babcock M.C., Kaplan J. The yeast frataxin homologue mediates mitochondrial iron efflux. Evidence for a mitochondrial iron cycle. J Biol Chem. 274:1999;4497-4499. Clear evidence is presented for frataxin loss of Fe transporting function leading to mitochondrial damage and FA.
51. ••]) underscore the need of mitochondria for SOD2 (manganese SOD) activity, and highlight the mitochondria as a major source of potentially lethal superoxide generation.
52. •].