Essential Metals in the Brain and the Application of Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry for their Detection
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Folarin, O. R., Olopade, F. E., & Olopade, J. O. . (2021). Essential Metals in the Brain and the Application of Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry for their Detection. Nigerian Journal of Physiological Sciences, 36(2), 123–147. https://doi.org/10.54548/njps.v36i2.1

Abstract

Metals are natural component of the ecosystem present throughout the layers of atmosphere; their abundant expression in the brain indicates their importance in the central nervous system (CNS). Within the brain tissue, their distribution is highly compartmentalized, the pattern of which is determined by their primary roles. Bio-imaging of the brain to reveal spatial distribution of metals within specific regions has provided a unique understanding of brain biochemistry and architecture, linking both the structures and the functions through several metal mediated activities. Bioavailability of essential trace metal is needed for normal brain function. However, disrupted metal homeostasis can influence several biochemical pathways in different fields of metabolism and cause characteristic neurological disorders with a typical disease process usually linked with aberrant metal accumulations. In this review we give a brief overview of roles of key essential metals (Iron, Copper and Zinc) including their molecular mechanisms and bio-distribution in the brain as well as their possible involvement in the pathogenesis of related neurodegenerative diseases. In addition, we also reviewed recent applications of Laser Ablation Inductively Couple Plasma Mass Spectrophotometry (LA-ICP-MS) in the detection of both toxic and essential metal dyshomeostasis in neuroscience research and other related brain diseases

https://doi.org/10.54548/njps.v36i2.1
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References

Abboud, S., & Haile, D. J. (2000). A novel mammalian iron-regulated protein involved in intracellular iron metabolism. Journal of Biological Chemistry, 275(26), 19906-19912.

Aizenman, E., Stout, A. K., Hartnett, K. A., Dineley, K. E., McLaughlin, B., & Reynolds, I. J. (2000). Induction of neuronal apoptosis by thiol oxidation: putative role of intracellular zinc release. Journal of neurochemistry, 75(5), 1878-1888.

An, W. L., Bjorkdahl, C., Liu, R., Cowburn, R. F., Winblad, B., & Pei, J. J. (2005). Mechanism of zinc‐induced phosphorylation of p70 S6 kinase and glycogen synthase kinase 3β in SH‐SY5Y neuroblastoma cells. Journal of neurochemistry, 92(5), 1104-1115.

Anderson, J. G., & Erikson, K. M. (2011). The importance of trace elements for neurological function. In Handbook of behavior, food and nutrition (pp. 423-439). Springer, New York, NY.

Andrási, E., Igaz, S., Szoboszlai, N., Farkas, É., & Ajtony, Z. (1999). Several methods to determine heavy metals in the human brain. Spectrochimica Acta Part B: Atomic Spectroscopy, 54(5), 819-825.

Aoki, S., Okada, Y., Nishimura, K., Barkovich, A. J., Kjos, B. O., Brasch, R. C., & Norman, D. (1989). Normal deposition of brain iron in childhood and adolescence: MR imaging at 1.5 T. Radiology, 172(2), 381-385.

Arruti, A., Fernández-Olmo, I., & Irabien, Á. (2010). Evaluation of the contribution of local sources to trace metals levels in urban PM2. 5 and PM10 in the Cantabria region (Northern Spain). Journal of Environmental Monitoring, 12(7), 1451-1458.

Aschner, M., & Aschner, J. L. (1990). Manganese transport across the blood-brain barrier: relationship to iron homeostasis. Brain research bulletin, 24(6), 857-860.

Ayton, S., Lei, P., Hare, D. J., Duce, J. A., George, J. L., Adlard, P. A., ... & Bush, A. I. (2015). Parkinson's disease iron deposition caused by nitric oxide-induced loss of β-amyloid precursor protein. Journal of Neuroscience, 35(8), 3591-3597.

Bartzokis, G., Tishler, T. A., Lu, P. H., Villablanca, P., Altshuler, L. L., Carter, M., ... & Mintz, J. (2007). Brain ferritin iron may influence age-and gender-related risks of neurodegeneration. Neurobiology of aging, 28(3), 414-423.

Beard, J. L., Connor, J. R., & Jones, B. C. (1993). Iron in the brain. Nutrition reviews, 51(6), 157-170.

Becker, J. S., & Salber, D. (2010). New mass spectrometric tools in brain research. TrAC Trends in Analytical Chemistry, 29(9), 966-979.

Becker, J. S., & Jakubowski, N. (2009). The synergy of elemental and biomolecular mass spectrometry: new analytical strategies in life sciences. Chemical Society Reviews, 38(7), 1969-1983.

Becker, J. S., & Jakubowski, N. (2009). The synergy of elemental and biomolecular mass spectrometry: new analytical strategies in life sciences. Chemical Society Reviews, 38(7), 1969-1983.

Becker, J. S., Boulyga, S. F., Becker, J. S., Pickhardt, C., Damoc, E., &Przybylski, M. (2003). Structural identification and quantification of protein phosphorylations after gel electrophoretic separation using Fourier transform ion cyclotron resonance mass spectrometry and laser ablation inductively coupled plasma mass spectrometry. International journal of mass spectrometry, 228(2-3), 985-997.

Becker, J. S., Gorbunoff, A., Zoriy, M., Izmer, A., & Kayser, M. (2006). Evidence of near-field laser ablation inductively coupled plasma mass spectrometry (NF-LA-ICP-MS) at nanometre scale for elemental and isotopic analysis on gels and biological samples. Journal of analytical atomic spectrometry, 21(1), 19-25.

Becker, J. S., Kumtabtim, U., Wu, B., Steinacker, P., Otto, M., & Matusch, A. (2012). Mass spectrometry imaging (MSI) of metals in mouse spinal cord by laser ablation ICP-MS. Metallomics, 4(3), 284-288.

Becker, J. S., Matusch, A., Depboylu, C., Dobrowolska, J., & Zoriy, M. V. (2007). Quantitative imaging of selenium, copper, and zinc in thin sections of biological tissues (Slugs− Genus Arion) measured by laser ablation inductively coupled plasma mass spectrometry. Analytical chemistry, 79(16), 6074-6080.

Becker, J. S., Zoriy, M. V., Dehnhardt, M., Pickhardt, C., & Zilles, K. (2005). Copper, zinc, phosphorus and sulfur distribution in thin section of rat brain tissues measured by laser ablation inductively coupled plasma mass spectrometry: possibility for small-size tumor analysis. Journal of analytical atomic spectrometry, 20(9), 912-917.

Becker, J. S., Zoriy, M., Becker, J. S., Pickhardt, C., & Przybylski, M. (2004). Determination of phosphorus and metals in human brain proteins after isolation by gel electrophoresis by laser ablation inductively coupled plasma source mass spectrometry. Journal of Analytical Atomic Spectrometry, 19(1), 149-152.

Belaidi, A. A., & Bush, A. I. (2016). Iron neurochemistry in Alzheimer's disease and Parkinson's disease: targets for therapeutics. Journal of neurochemistry, 139, 179-197.

Besser, L., Chorin, E., Sekler, I., Silverman, W. F., Atkin, S., Russell, J. T., & Hershfinkel, M. (2009). Synaptically released zinc triggers metabotropic signaling via a zinc-sensing receptor in the hippocampus. Journal of Neuroscience, 29(9), 2890-2901.

Bhat, S. A. (2019). Heavy metal toxicity and their harmful effects on living organisms–a review. International Journal of Medical Science And Diagnosis Research, 3(1).

Bhat, S. A., Hassan, T., Majid, S., Ashraf, R., & Kuchy, S. (2017). Environmental Pollution as Causative Agent for Cancer-A Review. Cancer Clin. Res. Rep, 1(3).

Björkdahl, C., Sjögren, M. J., Winblad, B., & Pei, J. J. (2005). Zinc induces neurofilament phosphorylation independent of p70 S6 kinase in N2a cells. Neuroreport, 16(6), 591-595.

Bjørklund, G., Hofer, T., Nurchi, V. M., & Aaseth, J. (2019). Iron and other metals in the pathogenesis of Parkinson's disease: Toxic effects and possible detoxification. Journal of inorganic biochemistry, 199, 110717.

Boaru, S. G., Merle, U., Uerlings, R., Zimmermann, A., Weiskirchen, S., Matusch, A., ... & Weiskirchen, R. (2014). Simultaneous monitoring of cerebral metal accumulation in an experimental model of Wilson’s disease by laser ablation inductively coupled plasma mass spectrometry. BMC neuroscience, 15(1), 1-14.

Bodovitz, S., Falduto, M. T., Frail, D. E., & Klein, W. L. (1995). Iron levels modulate α‐secretase cleavage of amyloid precursor protein. Journal of neurochemistry, 64(1), 307-315.

Bogdanov, M., Brown Jr, R. H., Matson, W., Smart, R., Hayden, D., O’Donnell, H., ... & Cudkowicz, M. (2000). Increased oxidative damage to DNA in ALS patients. Free Radical Biology and Medicine, 29(7), 652-658.

Bolognin, S., Messori, L., Drago, D., Gabbiani, C., Cendron, L., & Zatta, P. (2011). Aluminum, copper, iron and zinc differentially alter amyloid-Aβ1–42 aggregation and toxicity. The international journal of biochemistry & cell biology, 43(6), 877-885.

Bossy-Wetzel, E., Talantova, M. V., Lee, W. D., Schölzke, M. N., Harrop, A., Mathews, E., ... & Lipton, S. A. (2004). Crosstalk between nitric oxide and zinc pathways to neuronal cell death involving mitochondrial dysfunction and p38-activated K+ channels. Neuron, 41(3), 351-365.

Brewer, G. J., Kanzer, S. H., Zimmerman, E. A., Molho, E. S., Celmins, D. F., Heckman, S. M., & Dick, R. (2010). Subclinical zinc deficiency in Alzheimer’s disease and Parkinson’s disease. American Journal of Alzheimer's Disease & Other Dementias®, 25(7), 572-575.

Briggs, D., & Grant, J. T. (Eds.). (2012). Surface analysis by Auger and X-ray photoelectron spectroscopy. SurfaceSpectra.

Brown, D. R. (2009). Metal binding to alpha-synuclein peptides and its contribution to toxicity. Biochemical and biophysical research communications, 380(2), 377-381.

Bulk, M., Abdelmoula, W. M., Nabuurs, R. J., van der Graaf, L. M., Mulders, C. W., Mulder, A. A., ... & van der Weerd, L. (2018). Postmortem MRI and histology demonstrate differential iron accumulation and cortical myelin organization in early-and late-onset Alzheimer's disease. Neurobiology of aging, 62, 231-242.

Burdette, S. C., & Lippard, S. J. (2003). Meeting of the minds: metalloneurochemistry. Proceedings of the National Academy of Sciences, 100(7), 3605-3610.

Burdo, J. R., Menzies, S. L., Simpson, I. A., Garrick, L. M., Garrick, M. D., Dolan, K. G., ... & Connor, J. R. (2001). Distribution of divalent metal transporter 1 and metal transport protein 1 in the normal and Belgrade rat. Journal of neuroscience research, 66(6), 1198-1207.

Bush, A. I., Masters, C. L., & Tanzi, R. E. (2003). Copper, β-amyloid, and Alzheimer's disease: tapping a sensitive connection. Proceedings of the National Academy of Sciences, 100(20), 11193-11194.

Bush, A. I., Pettingell Jr, W. H., Paradis, M. D., & Tanzi, R. E. (1994). Modulation of A beta adhesiveness and secretase site cleavage by zinc. Journal of Biological Chemistry, 269(16), 12152-12158.

Bush, A. I., Pettingell, W. H., Multhaup, G., d Paradis, M., Vonsattel, J. P., Gusella, J. F., ... & Tanzi, R. E. (1994). Rapid induction of Alzheimer A beta amyloid formation by zinc. Science, 265(5177), 1464-1467.

Butterfield, D. A., Drake, J., Pocernich, C., & Castegna, A. (2001). Evidence of oxidative damage in Alzheimer's disease brain: central role for amyloid β-peptide. Trends in molecular medicine, 7(12), 548-554.

Calderón-Garcidueñas, L., Kavanaugh, M., Block, M., D'Angiulli, A., Delgado-Chávez, R., Torres-Jardón, R., ... & Diaz, P. (2012). Neuroinflammation, hyperphosphorylated tau, diffuse amyloid plaques, and down-regulation of the cellular prion protein in air pollution exposed children and young adults. Journal of Alzheimer's disease, 28(1), 93-107.

Caldwell, J. H., Klevanski, M., Saar, M., & Müller, U. C. (2013). Roles of the amyloid precursor protein family in the peripheral nervous system. Mechanisms of development, 130(6-8), 433-446.

Cammack, R., Wrigglesworth, J. M., & Baum, H. (1990). Iron-dependent enzymes in mammalian systems. In Iron transport and storage (p. 17). CRC Press, Boca Raton.

Cardoso, B. R., Cominetti, C., & Cozzolino, S. M. F. (2013). Importance and management of micronutrient deficiencies in patients with Alzheimer’s disease. Clinical Interventions in Aging, 8, 531.

Carmona, A., Deves, G., & Ortega, R. (2008). Quantitative micro-analysis of metal ions in subcellular compartments of cultured dopaminergic cells by combination of three ion beam techniques. Analytical and bioanalytical chemistry, 390(6), 1585-1594.

Carrı̀, M. T., Ferri, A., Cozzolino, M., Calabrese, L., & Rotilio, G. (2003). Neurodegeneration in amyotrophic lateral sclerosis: the role of oxidative stress and altered homeostasis of metals. Brain research bulletin, 61(4), 365-374.

Castellani, R. J., Moreira, P. I., Perry, G., & Zhu, X. (2012). The role of iron as a mediator of oxidative stress in Alzheimer disease. Biofactors, 38(2), 133-138.

Chan, A., & Shea, T. B. (2006). Dietary and genetically-induced oxidative stress alter tau phosphorylation: influence of folate and apolipoprotein E deficiency. Journal of Alzheimer's Disease, 9(4), 399-405.

Chandra, S., Parker, D. J., Barth, R. F., & Pannullo, S. C. (2016). Quantitative imaging of magnesium distribution at single-cell resolution in brain tumors and infiltrating tumor cells with secondary ion mass spectrometry (SIMS). Journal of neuro-oncology, 127(1), 33-41.

Chen, P., Miah, M. R., & Aschner, M. (2016). Metals and neurodegeneration. F1000Research, 5.

Choi, B. S., & Zheng, W. (2009). Copper transport to the brain by the blood-brain barrier and blood-CSF barrier. Brain research, 1248, 14-21.

Connor, J. R. (2018). Proteins of iron regulation in the brain in Alzheimer's disease. In Iron and human disease (pp. 365-394). CRC press.

Connor, J. R., Boeshore, K. L., Benkovic, S. A., & Menzies, S. L. (1994). Isoforms of ferritin have a specific cellular distribution in the brain. Journal of neuroscience research, 37(4), 461-465.

Connor, J. R., Snyder, B. S., Arosio, P., Loeffler, D. A., & LeWitt, P. (1995). A quantitative analysis of isoferritins in select regions of aged, parkinsonian, and Alzheimer's diseased brains. Journal of neurochemistry, 65(2), 717-724.

Connor, J. R., Snyder, B. S., Beard, J. L., Fine, R. E., & Mufson, E. J. (1992). Regional distribution of iron and iron‐regulatory proteins in the brain in aging and Alzheimer's disease. Journal of neuroscience research, 31(2), 327-335.

Connor, J. R., Tucker, P., Johnson, M., & Snyder, B. (1993). Ceruloplasmin levels in the human superior temporal gyrus in aging and Alzheimer's disease. Neuroscience letters, 159(1-2), 88-90.

Costa-Mallen, P., Gatenby, C., Friend, S., Maravilla, K. R., Hu, S. C., Cain, K. C., ... & Anzai, Y. (2017). Brain iron concentrations in regions of interest and relation with serum iron levels in Parkinson disease. Journal of the neurological sciences, 378, 38-44.

Costa-Mallen, P., Zabetian, C. P., Agarwal, P., Hu, S. C., Yearout, D., Samii, A., ... & Checkoway, H. (2015). Haptoglobin phenotype modifies serum iron levels and the effect of smoking on Parkinson disease risk. Parkinsonism & related disorders, 21(9), 1087-1092.

Cousins, R. J., Liuzzi, J. P., & Lichten, L. A. (2006). Mammalian zinc transport, trafficking, and signals. Journal of Biological Chemistry, 281(34), 24085-24089.

Craelius, W., Migdal, M. W., Luessenhop, C. P., Sugar, A., & Mihalakis, I. (1982). Iron deposits surrounding multiple sclerosis plaques. Archives of pathology & laboratory medicine, 106(8), 397-399.

Crichton, R. R., Dexter, D. T., & Ward, R. J. (2008). Metal based neurodegenerative diseases—from molecular mechanisms to therapeutic strategies. Coordination Chemistry Reviews, 252(10-11), 1189-1199.

Crow, J. P., Sampson, J. B., Zhuang, Y., Thompson, J. A., & Beckman, J. S. (1997). Decreased zinc affinity of amyotrophic lateral sclerosis‐associated superoxide dismutase mutants leads to enhanced catalysis of tyrosine nitration by peroxynitrite. Journal of neurochemistry, 69(5), 1936-1944.

Culotta, V. C., Yang, M., & O'Halloran, T. V. (2006). Activation of superoxide dismutases: putting the metal to the pedal. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1763(7), 747-758.

Davies, K. M., Hare, D. J., Bohic, S., James, S. A., Billings, J. L., Finkelstein, D. I., ... & Double, K. L. (2015). Comparative study of metal quantification in neurological tissue using laser ablation-inductively coupled plasma-mass spectrometry imaging and X-ray fluorescence microscopy. Analytical chemistry, 87(13), 6639-6645.

Davies, K. M., Hare, D. J., Cottam, V., Chen, N., Hilgers, L., Halliday, G., ... & Double, K. L. (2013). Localization of copper and copper transporters in the human brain. Metallomics, 5(1), 43-51.

Davies, P., Moualla, D., & Brown, D. R. (2011). Alpha-synuclein is a cellular ferrireductase. PloS one, 6(1), e15814..

De Rijk, M. D., Tzourio, C., Breteler, M. M., Dartigues, J. F., Amaducci, L., Lopez-Pousa, S., ... & Rocca, W. A. (1997). Prevalence of parkinsonism and Parkinson's disease in Europe: the EUROPARKINSON Collaborative Study. European Community Concerted Action on the Epidemiology of Parkinson's disease. Journal of Neurology, Neurosurgery & Psychiatry, 62(1), 10-15.

DeBenedictis, C. A., Raab, A., Ducie, E., Howley, S., Feldmann, J., & Grabrucker, A. M. (2020). Concentrations of Essential Trace Metals in the Brain of Animal Species—A Comparative Study. Brain sciences, 10(7), 460.

Deibel, M. A., Ehmann, W. D., & Markesbery, W. R. (1996). Copper, iron, and zinc imbalances in severely degenerated brain regions in Alzheimer's disease: possible relation to oxidative stress. Journal of the neurological sciences, 143(1-2), 137-142.

Deng, H. X., Hentati, A., Tainer, J. A., Iqbal, Z., Cayabyab, A., Hung, W. Y., ... & Roos, R. P. (1993). Amyotrophic lateral sclerosis and structural defects in Cu, Zn superoxide dismutase. Science, 261(5124), 1047-1051.

Depboylu, C., Matusch, A., Tribl, F., Zoriy, M., Michel, P. P., Riederer, P., ... & Höglinger, G. U. (2007). Glia protects neurons against extracellular human neuromelanin. Neurodegenerative Diseases, 4(2-3), 218-226.

Devi, L., Raghavendran, V., Prabhu, B. M., Avadhani, N. G., & Anandatheerthavarada, H. K. (2008). Mitochondrial import and accumulation of α-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain. Journal of Biological Chemistry, 283(14), 9089-9100.

Dexter, D. T., Carayon, A., Javoy-Agid, F., Agid, Y., Wells, F. R., Daniel, S. E., ... & Marsden, C. D. (1991). Alterations in the levels of iron, ferritin and other trace metals in Parkinson's disease and other neurodegenerative diseases affecting the basal ganglia. Brain, 114(4), 1953-1975.

Dobrowolska, J., Dehnhardt, M., Matusch, A., Zoriy, M., Palomero-Gallagher, N., Koscielniak, P., ... & Becker, J. S. (2008). Quantitative imaging of zinc, copper and lead in three distinct regions of the human brain by laser ablation inductively coupled plasma mass spectrometry. Talanta, 74(4), 717-723.

Donovan, A., Brownlie, A., Zhou, Y., Shepard, J., Pratt, S. J., Moynihan, J., ... & Zon, L. I. (2000). Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature, 403(6771), 776-781.

Dunn, L. L., Rahmanto, Y. S., & Richardson, D. R. (2007). Iron uptake and metabolism in the new millennium. Trends in cell biology, 17(2), 93-100.

Durrant, S. F., & Ward, N. I. (2005). Recent biological and environmental applications of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Journal of Analytical Atomic Spectrometry, 20(9), 821-829.

Dwork, A. J., Lawler, G., Zybert, P. A., Durkin, M., Osman, M., Willson, N., & Barkai, A. I. (1990). An autoradiographic study of the uptake and distribution of iron by the brain of the young rat. Brain Research, 518(1-2), 31-39.

Eid, R., Arab, N. T., & Greenwood, M. T. (2017). Iron mediated toxicity and programmed cell death: A review and a re-examination of existing paradigms. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1864(2), 399-430.

Eisenstein, R. S. (2000). Iron regulatory proteins and the molecular control of mammalian iron metabolism. Annual review of nutrition, 20(1), 627-662.

Elseweidy, M. M., & Abd El-Baky, A. E. (2008). Effect of dietary iron overload in rat brain: oxidative stress, neurotransmitter level and serum metal ion in relation to neurodegenerative disorders.

Emwas, A. H. M., Al‐Talla, Z. A., Guo, X., Al‐Ghamdi, S., & Al‐Masri, H. T. (2013). Utilizing NMR and EPR spectroscopy to probe the role of copper in prion diseases. Magnetic Resonance in Chemistry, 51(5), 255-268.

Estévez, A. G., Crow, J. P., Sampson, J. B., Reiter, C., Zhuang, Y., Richardson, G. J., ... & Beckman, J. S. (1999). Induction of Nitric Oxide--Dependent Apoptosis in Motor Neurons by Zinc-Deficient Superoxide Dismutase. Science, 286(5449), 2498-2500.

Everett, J., Collingwood, J. F., Tjendana-Tjhin, V., Brooks, J., Lermyte, F., Plascencia-Villa, G., ... & Telling, N. D. (2018). Nanoscale synchrotron X-ray speciation of iron and calcium compounds in amyloid plaque cores from Alzheimer's disease subjects. Nanoscale, 10(25), 11782-11796.

Faucheux, B. A., Nillesse, N., Damier, P., Spik, G., Mouatt-Prigent, A., Pierce, A., ... & Agid, Y. (1995). Expression of lactoferrin receptors is increased in the mesencephalon of patients with Parkinson disease. Proceedings of the National Academy of Sciences, 92(21), 9603-9607.

Feng, T. Y., Yang, Z. K., Zheng, J. W., Xie, Y., Li, D. W., Murugan, S. B., ... & Li, H. Y. (2015). Examination of metabolic responses to phosphorus limitation via proteomic analyses in the marine diatom Phaeodactylum tricornutum. Scientific Reports, 5(1), 1-10.

Ferrante, R. J., Browne, S. E., Shinobu, L. A., Bowling, A. C., Baik, M. J., MacGarvey, U., ... & Beal, M. F. (1997). Evidence of increased oxidative damage in both sporadic and familial amyotrophic lateral sclerosis. Journal of neurochemistry, 69(5), 2064-2074.

Ferrante, R. J., Browne, S. E., Shinobu, L. A., Bowling, A. C., Baik, M. J., MacGarvey, U., ... & Beal, M. F. (1997). Evidence of increased oxidative damage in both sporadic and familial amyotrophic lateral sclerosis. Journal of neurochemistry, 69(5), 2064-2074.

Ferreira, K. P. Z., Oliveira, S. R., Kallaur, A. P., Kaimen-Maciel, D. R., Lozovoy, M. A. B., de Almeida, E. R. D., ... & Simão, A. N. C. (2017). Disease progression and oxidative stress are associated with higher serum ferritin levels in patients with multiple sclerosis. Journal of the neurological sciences, 373, 236-241.

Flora, S. J., & Pachauri, V. (2010). Chelation in metal intoxication. International journal of environmental research and public health, 7(7), 2745-2788.

Folarin, O. R., Snyder, A. M., Peters, D. G., Olopade, F., Connor, J. R., & Olopade, J. O. (2017). Brain metal distribution and neuro-inflammatory profiles after chronic vanadium administration and withdrawal in mice. Frontiers in neuroanatomy, 11, 58.

Forge, J. K., Pedchenko, T. V., & Le Vine, S. M. (1998). Iron deposits in the central nervous system of SJL mice with experimental allergic encephalomyelitis. Life sciences, 63(25), 2271-2284.

Forsleff, L., Schauss, A. G., Bier, I. D., & Stuart, S. (1999). Evidence of functional zinc deficiency in Parkinson's disease. The Journal of Alternative and Complementary Medicine, 5(1), 57-64.

Frederickson CJ, Bush AI (2001) Synaptically released zinc: physiological functions and pathological effects. Biometals 14(3-4):353-366.

Frederickson, C. J., Koh, J. Y., & Bush, A. I. (2005). The neurobiology of zinc in health and disease. Nature Reviews Neuroscience, 6(6), 449-462.

Frederickson, C. J., Maret, W., & Cuajungco, M. P. (2004). Zinc and excitotoxic brain injury: a new model. The Neuroscientist, 10(1), 18-25.

Fu, S., Jiang, W., & Zheng, W. (2015). Age-dependent increase of brain copper levels and expressions of copper regulatory proteins in the subventricular zone and choroid plexus. Frontiers in molecular neuroscience, 8, 22.

Fu, X., Zeng, A., Zheng, W., & Du, Y. (2014). Upregulation of zinc transporter 2 in the blood–CSF barrier following lead exposure. Experimental Biology and Medicine, 239(2), 202-212.

Fukada, T., Yamasaki, S., Nishida, K., Murakami, M., & Hirano, T. (2011). Zinc homeostasis and signaling in health and diseases. JBIC Journal of Biological Inorganic Chemistry, 16(7), 1123-1134.

Funke, C., Schneider, S. A., Berg, D., & Kell, D. B. (2013). Genetics and iron in the systems biology of Parkinson’s disease and some related disorders. Neurochemistry international, 62(5), 637-652.

Gaggelli, E., Kozlowski, H., Valensin, D., & Valensin, G. (2006). Copper homeostasis and neurodegenerative disorders (Alzheimer's, prion, and Parkinson's diseases and amyotrophic lateral sclerosis). Chemical reviews, 106(6), 1995-2044.

Garza-Lombó, C., Posadas, Y., Quintanar, L., Gonsebatt, M. E., & Franco, R. (2018). Neurotoxicity linked to dysfunctional metal ion homeostasis and xenobiotic metal exposure: redox signaling and oxidative stress. Antioxidants & redox signaling, 28(18), 1669-1703.

Gemmati, D., Tognazzo, S., Catozzi, L., Federici, F., De Palma, M., Gianesini, S., ... & Zamboni, P. (2006). Influence of gene polymorphisms in ulcer healing process after superficial venous surgery. Journal of vascular surgery, 44(3), 554-562.

Gemmati, D., Zeri, G., Orioli, E., De Gaetano, F. E., Salvi, F., Bartolomei, I., ... & Zamboni, P. (2012). Polymorphisms in the genes coding for iron binding and transporting proteins are associated with disability, severity, and early progression in multiple sclerosis. BMC medical genetics, 13(1), 1-13.

Goodall, E. F., Haque, M. S., & Morrison, K. E. (2008). Increased serum ferritin levels in amyotrophic lateral sclerosis (ALS) patients. Journal of neurology, 255(11), 1652-1656.

Goto, J. J., Zhu, H., Sanchez, R. J., Nersissian, A., Gralla, E. B., Valentine, J. S., & Cabelli, D. E. (2000). Loss of in vitro metal ion binding specificity in mutant copper-zinc superoxide dismutases associated with familial amyotrophic lateral sclerosis. Journal of Biological Chemistry, 275(2), 1007-1014.

Grilli, M., Goffi, F., Memo, M., & Spano, P. (1996). Interleukin-1β and glutamate activate the NF-κB/Rel binding site from the regulatory region of the amyloid precursor protein gene in primary neuronal cultures. Journal of Biological Chemistry, 271(25), 15002-15007.

Grochowski, C., Blicharska, E., Krukow, P., Jonak, K., Maciejewski, M., Szczepanek, D., ... & Maciejewski, R. (2019). Analysis of trace elements in human brain: its aim, methods, and concentration levels. Frontiers in chemistry, 7, 115.

Grochowski, C., Blicharska, E., Krukow, P., Jonak, K., Maciejewski, M., Szczepanek, D., ... & Maciejewski, R. (2019). Analysis of trace elements in human brain: its aim, methods, and concentration levels. Frontiers in chemistry, 7, 115.

Guerreiro, C., Silva, B., Crespo, Â. C., Marques, L., Costa, S., Timóteo, Â., ... & Costa, L. (2015). Decrease in APP and CP mRNA expression supports impairment of iron export in Alzheimer's disease patients. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1852(10), 2116-2122.

Ha, C., Ryu, J., & Park, C. B. (2007). Metal ions differentially influence the aggregation and deposition of Alzheimer's β-amyloid on a solid template. Biochemistry, 46(20), 6118-6125.

Hadzhieva, M., Kirches, E., Wilisch-Neumann, A., Pachow, D., Wallesch, M., Schoenfeld, P., ... & Mawrin, C. (2013). Dysregulation of iron protein expression in the G93A model of amyotrophic lateral sclerosis. Neuroscience, 230, 94-101.

Hametner, S., Wimmer, I., Haider, L., Pfeifenbring, S., Brück, W., & Lassmann, H. (2013). Iron and neurodegeneration in the multiple sclerosis brain. Annals of neurology, 74(6), 848-861.

Hamza, I., & Gitlin, J. D. (2002). Copper chaperones for cytochrome c oxidase and human disease. Journal of bioenergetics and biomembranes, 34(5), 381-388.

Hamza, I., Faisst, A., Prohaska, J., Chen, J., Gruss, P., & Gitlin, J. D. (2001). The metallochaperone Atox1 plays a critical role in perinatal copper homeostasis. Proceedings of the National Academy of Sciences, 98(12), 6848-6852.

Hamza, I., Prohaska, J., & Gitlin, J. D. (2003). Essential role for Atox1 in the copper-mediated intracellular trafficking of the Menkes ATPase. Proceedings of the National Academy of Sciences, 100(3), 1215-1220.

Hare, D. J., George, J. L., Grimm, R., Wilkins, S., Adlard, P. A., Cherny, R. A., ... & Doble, P. (2010). Three-dimensional elemental bio-imaging of Fe, Zn, Cu, Mn and P in a 6-hydroxydopamine lesioned mouse brain. Metallomics, 2(11), 745-753.

Hare, D. J., Kysenius, K., Paul, B., Knauer, B., Hutchinson, R. W., O'Connor, C., ... & Doble, P. A. (2017). Imaging metals in brain tissue by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). Journal of visualized experiments: JoVE, (119).

Hare, D. J., Lee, J. K., Beavis, A. D., van Gramberg, A., George, J., Adlard, P. A., ... & Doble, P. A. (2012). Three-dimensional atlas of iron, copper, and zinc in the mouse cerebrum and brainstem. Analytical chemistry, 84(9), 3990-3997.

Hare, D. J., Lei, P., Ayton, S., Roberts, B. R., Grimm, R., George, J. L., ... & Doble, P. A. (2014). An iron–dopamine index predicts risk of parkinsonian neurodegeneration in the substantia nigra pars compacta. Chemical Science, 5(6), 2160-2169.

Hare, D. J., Paul, B., & Doble, P. A. (2017). Imaging Metals in the Brain by Laser Ablation–Inductively Coupled Plasma-Mass Spectrometry. In Metals in the Brain (pp. 33-50). Humana Press, New York, NY.

Hare, D. J., Paul, B., & Doble, P. A. (2017). Imaging Metals in the Brain by Laser Ablation–Inductively Coupled Plasma-Mass Spectrometry. In Metals in the Brain (pp. 33-50). Humana Press, New York, NY.

Hare, D. J., Raven, E. P., Roberts, B. R., Bogeski, M., Portbury, S. D., McLean, C. A., ... & Doble, P. A. (2016). Laser ablation-inductively coupled plasma-mass spectrometry imaging of white and gray matter iron distribution in Alzheimer's disease frontal cortex. NeuroImage, 137, 124-131.

Hare, D., Reedy, B., Grimm, R., Wilkins, S., Volitakis, I., George, J. L., ... & Doble, P. (2009). Quantitative elemental bio-imaging of Mn, Fe, Cu and Zn in 6-hydroxydopamine induced Parkinsonism mouse models. Metallomics, 1(1), 53-58.

Harris, E. D. (2001). Copper homeostasis: the role of cellular transporters. Nutrition reviews, 59(9), 281-285.

Hartung, H. P., Schäfer, B., Heininger, K., & Toyka, K. V. (1988). Suppression of experimental autoimmune neuritis by the oxygen radical scavengers superoxide dismutase and catalase. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society, 23(5), 453-460.

Hartwig, C., Zlatic, S. A., Wallin, M., Vrailas-Mortimer, A., Fahrni, C. J., & Faundez, V. (2019). Trafficking mechanisms of P-type ATPase copper transporters. Current opinion in cell biology, 59, 24-33.

Hattendorf, B., Latkoczy, C., & Günther, D. (2003). Peer reviewed: laser ablation-ICPMS.

Hentze, M. W., & Kühn, L. C. (1996). Molecular control of vertebrate iron metabolism: mRNA-based regulatory circuits operated by iron, nitric oxide, and oxidative stress. Proceedings of the national academy of sciences, 93(16), 8175-8182.

Hladky, S. B., & Barrand, M. A. (2016). Fluid and ion transfer across the blood–brain and blood–cerebrospinal fluid barriers; a comparative account of mechanisms and roles. Fluids and Barriers of the CNS, 13(1), 1-69.

Howland, D. S., Liu, J., She, Y., Goad, B., Maragakis, N. J., Kim, B., ... & Rothstein, J. D. (2002). Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS). Proceedings of the National Academy of Sciences, 99(3), 1604-1609.

Howland, D. S., Liu, J., She, Y., Goad, B., Maragakis, N. J., Kim, B., ... & Rothstein, J. D. (2002). Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS). Proceedings of the National Academy of Sciences, 99(3), 1604-1609.

Hozumi, I., Yamada, M., Uchida, Y., Ozawa, K., Takahashi, H., & Inuzuka, T. (2008). The expression of metallothioneins is diminished in the spinal cords of patients with sporadic ALS. Amyotrophic Lateral Sclerosis, 9(5), 294-298.

Huang, L., & Tepaamorndech, S. (2013). The SLC30 family of zinc transporters–a review of current understanding of their biological and pathophysiological roles. Molecular aspects of medicine, 34(2-3), 548-560.

Huang, X., Cuajungco, M. P., Atwood, C. S., Hartshorn, M. A., Tyndall, J. D., Hanson, G. R., ... & Bush, A. I. (1999). Cu (II) potentiation of Alzheimer Aβ neurotoxicity: correlation with cell-free hydrogen peroxide production and metal reduction. Journal of Biological Chemistry, 274(52), 37111-37116.

Hulet, S. W., Hess, E. J., Debinski, W., Arosio, P., Bruce, K., Powers, S., & Connor, J. R. (1999). Characterization and distribution of ferritin binding sites in the adult mouse brain. Journal of neurochemistry, 72(2), 868-874..

Hulet, S. W., Heyliger, S. O., Powers, S., & Connor, J. R. (2000). Oligodendrocyte progenitor cells internalize ferritin via clathrin‐dependent receptor mediated endocytosis. Journal of neuroscience research, 61(1), 52-60.

Hutchinson, R. W., Cox, A. G., McLeod, C. W., Marshall, P. S., Harper, A., Dawson, E. L., & Howlett, D. R. (2005). Imaging and spatial distribution of β-amyloid peptide and metal ions in Alzheimer’s plaques by laser ablation–inductively coupled plasma–mass spectrometry. Analytical biochemistry, 346(2), 225-233.

Hwang, E. M., Kim, S. K., Sohn, J. H., Lee, J. Y., Kim, Y., Kim, Y. S., & Mook-Jung, I. (2006). Furin is an endogenous regulator of α-secretase associated APP processing. Biochemical and biophysical research communications, 349(2), 654-659.

Ikeda, K., Hirayama, T., Takazawa, T., Kawabe, K., & Iwasaki, Y. (2012). Relationships between disease progression and serum levels of lipid, urate, creatinine and ferritin in Japanese patients with amyotrophic lateral sclerosis: a cross-sectional study. Internal medicine, 51(12), 1501-1508.

Ince, P. G., Shaw, P. J., Candy, J. M., Mantle, D., Tandon, L., Ehmann, W. D., & Markesbery, W. R. (1994). Iron, selenium and glutathione peroxidase activity are elevated in sporadic motor neuron disease. Neuroscience letters, 182(1), 87-90.

Iranmanesh, M., Iranmanesh, F., & Sadeghi, H. (2013). Serum level of iron, zinc and copper in patients with multiple sclerosis. Journal of Jahrom University of Medical Sciences, 10(4), 2.

Ishigaki, S., Niwa, J. I., Ando, Y., Yoshihara, T., Sawada, K. I., Doyu, M., ... & Sobue, G. (2002). Differentially expressed genes in sporadic amyotrophic lateral sclerosis spinal cords–screening by molecular indexing and subsequent cDNA microarray analysis. FEBS letters, 531(2), 354-358.

Jellinger, K., Kienzl, E., Rumpelmair, G., Riederer, P., Stachelberger, H., Ben‐Shachar, D., & Youdim, M. B. H. (1992). Iron‐melanin complex in substantia nigra of parkinsonian brains: an x‐ray microanalysis. Journal of neurochemistry, 59(3), 1168-1171.

Jeong, S. Y., Rathore, K. I., Schulz, K., Ponka, P., Arosio, P., & David, S. (2009). Dysregulation of iron homeostasis in the CNS contributes to disease progression in a mouse model of amyotrophic lateral sclerosis. Journal of Neuroscience, 29(3), 610-619.

Jomova, K., & Valko, M. (2011). Advances in metal-induced oxidative stress and human disease. Toxicology, 283(2-3), 65-87.

Jomova, K., Vondrakova, D., Lawson, M., & Valko, M. (2010). Metals, oxidative stress and neurodegenerative disorders. Molecular and cellular biochemistry, 345(1), 91-104.

Juneja, T., Pericak-Vance, M. A., Laing, N. G., Dave, S., & Siddique, T. (1997). Prognosis in familial amyotrophic lateral sclerosis: progression and survival in patients with glu100gly and ala4val mutations in Cu, Zn superoxide dismutase. Neurology, 48(1), 55-57.

Kambe, T., Fukue, K., Ishida, R., & Miyazaki, S. (2015). Overview of inherited zinc deficiency in infants and children. Journal of nutritional science and vitaminology, 61(Supplement), S44-S46.

Kaneko, M., Noguchi, T., Ikegami, S., Sakurai, T., Kakita, A., Toyoshima, Y., ... & Hozumi, I. (2015). Zinc transporters ZnT3 and ZnT6 are downregulated in the spinal cords of patients with sporadic amyotrophic lateral sclerosis. Journal of neuroscience research, 93(2), 370-379.

Kasarskis, E. J., Tandon, L., Lovell, M. A., & Ehmann, W. D. (1995). Aluminum, calcium, and iron in the spinal cord of patients with sporadic amyotrophic lateral sclerosis using laser microprobe mass spectroscopy: a preliminary study. Journal of the neurological sciences, 130(2), 203-208.

Kato, S., Takikawa, M., Nakashima, K., Hirano, A., Cleveland, D. W., Kusaka, H., ... & Ohama, E. (2000). New consensus research on neuropathological aspects of familial amyotrophic lateral sclerosis with superoxide dismutase 1 (SOD1) gene mutations: inclusions containing SOD1 in neurons and astrocytes. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders, 1(3), 163-184.

Khare, M., Singh, A. V., & Zamboni, P. (2014). Prospect of brain machine interface in motor disabilities: the future support for multiple sclerosis patient to improve quality of life. Annals of medical and health sciences research, 4(3), 305-312.

Kodama, H., Fujisawa, C., & Bhadhprasit, W. (2012). Inherited copper transport disorders: biochemical mechanisms, diagnosis, and treatment. Current drug metabolism, 13(3), 237-250.

Kozlowski, H., Łuczkowski, M., & Remelli, M. (2010). Prion proteins and copper ions. Biological and chemical controversies. Dalton Transactions, 39(28), 6371-6385.

Kozlowski, H., Luczkowski, M., Remelli, M., & Valensin, D. (2012). Copper, zinc and iron in neurodegenerative diseases (Alzheimer's, Parkinson's and prion diseases). Coordination Chemistry Reviews, 256(19-20), 2129-2141.

Kupershmidt, L., Weinreb, O., Amit, T., Mandel, S., Carri, M. T., & Youdim, M. B. (2009). Neuroprotective and neuritogenic activities of novel multimodal iron‐chelating drugs in motor‐neuron‐like NSC‐34 cells and transgenic mouse model of amyotrophic lateral sclerosis. The FASEB journal, 23(11), 3766-3779.

Lee, J., Kim, C. H., Kim, D. G., & Ahn, Y. S. (2009). Zinc Inhibits Amyloid β Production from Alzheimer's Amyloid Precursor Protein in SH-SY5Y Cells. The Korean journal of physiology & pharmacology: official journal of the Korean Physiological Society and the Korean Society of Pharmacology, 13(3), 195.

Lee, T. G., Park, J. W., Shon, H. K., Moon, D. W., Choi, W. W., Li, K., & Chung, J. H. (2008). Biochemical imaging of tissues by SIMS for biomedical applications. Applied Surface Science, 255(4), 1241-1248.

Leskovjan, A. C., Kretlow, A., Lanzirotti, A., Barrea, R., Vogt, S., & Miller, L. M. (2011). Increased brain iron coincides with early plaque formation in a mouse model of Alzheimer's disease. Neuroimage, 55(1), 32-38.

Leskovjan, A. C., Lanzirotti, A., & Miller, L. M. (2009). Amyloid plaques in PSAPP mice bind less metal than plaques in human Alzheimer's disease. NeuroImage, 47(4), 1215-1220.

Leveugle, B., Faucheux, B. A., Bouras, C., Nillesse, N., Spik, G., Hirsch, E. C., ... & Hof, P. R. (1996). Cellular distribution of the iron-binding protein lactotransferrin in the mesencephalon of Parkinson’s disease cases. Acta neuropathologica, 91(6), 566-572..

LeVine, S. M. (1997). Iron deposits in multiple sclerosis and Alzheimer's disease brains. Brain research, 760(1-2), 298-303.

Li Y, Jiao Q, Xu H, Du X, Shi L, Jia F, Jiang H (2017) Biometal dyshomeostasis and toxic metal accumulations in the development of Alzheimer’s disease. Frontiers in molecular neuroscience 10:339.

Li, K., & Reichmann, H. (2016). Role of iron in neurodegenerative diseases. Journal of Neural Transmission, 123(4), 389-399.

Linder, M. C., & Hazegh-Azam, M. (1996). Copper biochemistry and molecular biology. The American journal of clinical nutrition, 63(5), 797S-811S.

Ling, Y., Morgan, K., & Kalsheker, N. (2003). Amyloid precursor protein (APP) and the biology of proteolytic processing: relevance to Alzheimer’s disease. The international journal of biochemistry & cell biology, 35(11), 1505-1535.

Llanos, R. M., & Mercer, J. F. (2002). The molecular basis of copper homeostasis copper-related disorders. DNA and cell biology, 21(4), 259-270.

Localization of copper and copper transporters in the human brain. Metallomics 5(1):43-51.

Loeffler, D. A., Connor, J. R., Juneau, P. L., Snyder, B. S., Kanaley, L., DeMaggio, A. J., ... & LeWitt, P. A. (1995). Transferrin and iron in normal, Alzheimer's disease, and Parkinson's disease brain regions. Journal of neurochemistry, 65(2), 710-716.

Logroscino, G., Marder, K., Graziano, J., Freyer, G., Slavkovich, V., LoIacono, N., ... & Mayeux, R. (1997). Altered systemic iron metabolism in Parkinson's disease. Neurology, 49(3), 714-717.

Lohrke, J., Frisk, A. L., Frenzel, T., Schöckel, L., Rosenbruch, M., Jost, G., ... & Pietsch, H. (2017). Histology and gadolinium distribution in the rodent brain after the administration of cumulative high doses of linear and macrocyclic gadolinium-based contrast agents. Investigative radiology, 52(6), 324.

Lovell, M. A., Xiong, S., Xie, C., Davies, P., & Markesbery, W. R. (2004). Induction of hyperphosphorylated tau in primary rat cortical neuron cultures mediated by oxidative stress and glycogen synthase kinase-3. Journal of Alzheimer's Disease, 6(6), 659-671.

Lyons, T. J., Liu, H., Goto, J. J., Nersissian, A., Roe, J. A., Graden, J. A., ... & Valentine, J. S. (1996). Mutations in copper-zinc superoxide dismutase that cause amyotrophic lateral sclerosis alter the zinc binding site and the redox behavior of the protein. Proceedings of the National Academy of Sciences, 93(22), 12240-12244.

Macreadie, I. G. (2008). Copper transport and Alzheimer’s disease. European Biophysics Journal, 37(3), 295-300.

Madsen, E., & Gitlin, J. D. (2007). Copper and iron disorders of the brain. Annu. Rev. Neurosci., 30, 317-337.

Majumdar, S., Peralta-Videa, J. R., Castillo-Michel, H., Hong, J., Rico, C. M., & Gardea-Torresdey, J. L. (2012). Applications of synchrotron μ-XRF to study the distribution of biologically important elements in different environmental matrices: A review. Analytica chimica acta, 755, 1-16.

Marchetti, C. (2003). Molecular targets of lead in brain neurotoxicity. Neurotoxicity research, 5(3), 221-235.

Markesbery, W. R., Ehmann, W. D., Candy, J. M., Ince, P. G., Shaw, P. J., Tandon, L., & Deibel, M. A. (1995). Neutron activation analysis of trace elements in motor neuron disease spinal cord. Neurodegeneration, 4(4), 383-390.

Martin, L. J., Price, A. C., Kaiser, A., Shaikh, A. Y., & Liu, Z. (2000). Mechanisms for neuronal degeneration in amyotrophic lateral sclerosis and in models of motor neuron death. International journal of molecular medicine, 5(1), 3-16.

Masaldan, S., Clatworthy, S. A., Gamell, C., Meggyesy, P. M., Rigopoulos, A. T., Haupt, S., ... & Cater, M. A. (2018). Iron accumulation in senescent cells is coupled with impaired ferritinophagy and inhibition of ferroptosis. Redox biology, 14, 100-115.

Matusch, A., Depboylu, C., Palm, C., Wu, B., Höglinger, G. U., Schäfer, M. K. H., & Becker, J. S. (2010). Cerebral bioimaging of Cu, Fe, Zn, and Mn in the MPTP mouse model of Parkinson’s disease using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Journal of the American Society for Mass Spectrometry, 21(1), 161-171.

Maywald, M., Wessels, I., & Rink, L. (2017). Zinc signals and immunity. International journal of molecular sciences, 18(10), 2222.

Medici, V., & Huster, D. (2017). Animal models of Wilson disease. Handbook of clinical neurology, 142, 57-70.

Meloni, G., Faller, P., & Vaša, M. (2007). Redox silencing of copper in metal-linked neurodegenerative disorders: reaction of Zn7metallothionein-3 with Cu2+ ions. Journal of Biological Chemistry, 282(22), 16068-16078.

Mercer, J. F. (2001). The molecular basis of copper-transport diseases. Trends in molecular medicine, 7(2), 64-69.

Merle, U., & Weiskirchen, R. (2016). Wilson's disease: an inherited, silent, copper intoxication disease. Emj Neurol, 4, 74-83.

Miyazaki, I., & Asanuma, M. (2008). Dopaminergic neuron-specific oxidative stress caused by dopamine itself. Acta Medica Okayama, 62(3), 141-150.

Mo, Z. Y., Zhu, Y. Z., Zhu, H. L., Fan, J. B., Chen, J., & Liang, Y. (2009). Low micromolar zinc accelerates the fibrillization of human tau via bridging of Cys-291 and Cys-322. Journal of Biological Chemistry, 284(50), 34648-34657.

Mokgalaka, N. S., & Gardea‐Torresdey, J. L. (2006). Laser ablation inductively coupled plasma mass spectrometry: Principles and applications. Applied Spectroscopy Reviews, 41(2), 131-150.

Münch, G., Lüth, H. J., Wong, A., Arendt, T., Hirsch, E., Ravid, R. A., & Riederer, P. (2000). Crosslinking of α-synuclein by advanced glycation endproducts—an early pathophysiological step in Lewy body formation?. Journal of chemical neuroanatomy, 20(3-4), 253-257.

Nadal, R. C., Davies, P., Brown, D. R., & Viles, J. H. (2009). Evaluation of copper2+ affinities for the prion protein. Biochemistry, 48(38), 8929-8931.

Nadjar, Y., Gordon, P., Corcia, P., Bensimon, G., Pieroni, L., Meininger, V., & Salachas, F. (2012). Elevated serum ferritin is associated with reduced survival in amyotrophic lateral sclerosis. PloS one, 7(9), e45034.

Nagano, S., Satoh, M., Sumi, H., Fujimura, H., Tohyama, C., Yanagihara, T., & Sakoda, S. (2001). Reduction of metallothioneins promotes the disease expression of familial amyotrophic lateral sclerosis mice in a dose‐dependent manner. European Journal of Neuroscience, 13(7), 1363-1370.

Nakashima, K., Watanabe, Y., Kuno, N., Nanba, E., & Takahashi, K. (1995). Abnormality of Can superoxide dismutase (SOD1) activity in Japanese familial amyotrophic lateral sclerosis with two base pair deletion in the SODl gene. Neurology, 45(5), 1019-1019.

Nishihara, E., Furuyama, T., Yamashita, S., & Mori, N. (1998). Expression of copper trafficking genes in the mouse brain. Neuroreport, 9(14), 3259-3263.

Nishimura, N., Nishimura, H., Ghaffar, A., & Tohyama, C. (1992). Localization of metallothionein in the brain of rat and mouse. Journal of Histochemistry & Cytochemistry, 40(2), 309-315.

Noy, D., Solomonov, I., Sinkevich, O., Arad, T., Kjaer, K., & Sagi, I. (2008). Zinc-amyloid β interactions on a millisecond time-scale stabilize non-fibrillar Alzheimer-related species. Journal of the American Chemical Society, 130(4), 1376-1383.

Paik, S. R., SHIN, H. J., LEE, J. H., CHANG, C. S., & KIM, J. (1999). Copper (II)-induced self-oligomerization of α-synuclein. Biochemical Journal, 340(3), 821-828.

Pánik, J., Kopáni, M., Zeman, J., Ješkovský, M., Kaizer, J., & Povinec, P. P. (2018). Determination of metal elements concentrations in human brain tissues using PIXE and EDX methods. Journal of Radioanalytical and Nuclear Chemistry, 318(3), 2313-2319.

Parthasarathy, S., Yoo, B., McElheny, D., Tay, W., & Ishii, Y. (2014). Capturing a reactive state of amyloid aggregates. Journal of Biological Chemistry, 289(14), 9998-10010.

Pei, J. J., An, W. L., Zhou, X. W., Nishimura, T., Norberg, J., Benedikz, E., ... & Winblad, B. (2006). P70 S6 kinase mediates tau phosphorylation and synthesis. FEBS letters, 580(1), 107-114.

Pichler, R., Dunzinger, A., Wurm, G., Pichler, J., Weis, S., Nußbaumer, K., ... & Aigner, R. M. (2010). Is there a place for FET PET in the initial evaluation of brain lesions with unknown significance?. European journal of nuclear medicine and molecular imaging, 37(8), 1521-1528.

Pickhardt, C., Izmer, A. V., Zoriy, M. V., Schaumlöffel, D., & Becker, J. S. (2006). On-line isotope dilution in laser ablation inductively coupled plasma mass spectrometry using a microflow nebulizer inserted in the laser ablation chamber. International Journal of Mass Spectrometry, 248(3), 136-141.

Pierson, J., Norris, J. L., Aerni, H. R., Svenningsson, P., Caprioli, R. M., & Andrén, P. E. (2004). Molecular profiling of experimental Parkinson's disease: direct analysis of peptides and proteins on brain tissue sections by MALDI mass spectrometry. Journal of proteome research, 3(2), 289-295.

Pohl, H. R., Roney, N., & Abadin, H. G. (2015). 10 Metal Ions Affecting the Neurological System. In Metal Ions in Toxicology: Effects, Interactions, Interdependencies (pp. 247-262). De Gruyter.

Polishchuk, E. V., Merolla, A., Lichtmannegger, J., Romano, A., Indrieri, A., Ilyechova, E. Y., ... & Polishchuk, R. S. (2019). Activation of autophagy, observed in liver tissues from patients with Wilson disease and from ATP7B-deficient animals, protects hepatocytes from copper-induced apoptosis. Gastroenterology, 156(4), 1173-1189.

Popescu, B. F. G., George, M. J., Bergmann, U., Garachtchenko, A. V., Kelly, M. E., McCrea, R. P., ... & Nichol, H. (2009). Mapping metals in Parkinson's and normal brain using rapid-scanning x-ray fluorescence. Physics in Medicine & Biology, 54(3), 651.

Portbury, S. D., & Adlard, P. A. (2017). Zinc signal in brain diseases. International journal of molecular sciences, 18(12), 2506.

Portbury, S. D., Hare, D. J., Sgambelloni, C., Finkelstein, D. I., & Adlard, P. A. (2016). A time-course analysis of changes in cerebral metal levels following a controlled cortical impact. Metallomics, 8(2), 193-200.

Potter, D. (2008). A commercial perspective on the growth and development of the quadrupole ICP-MS market. Journal of Analytical Atomic Spectrometry, 23(5), 690-693.

Prashanth, L., Kattapagari, K. K., Chitturi, R. T., Baddam, V. R. R., & Prasad, L. K. (2015). A review on role of essential trace elements in health and disease. Journal of dr. ntr university of health sciences, 4(2), 75.

Puttaparthi, K., Gitomer, W. L., Krishnan, U., Son, M., Rajendran, B., & Elliott, J. L. (2002). Disease progression in a transgenic model of familial amyotrophic lateral sclerosis is dependent on both neuronal and non-neuronal zinc binding proteins. Journal of Neuroscience, 22(20), 8790-8796.

Puttaparthi, K., Wojcik, C., Rajendran, B., DeMartino, G. N., & Elliott, J. L. (2003). Aggregate formation in the spinal cord of mutant SOD1 transgenic mice is reversible and mediated by proteasomes. Journal of neurochemistry, 87(4), 851-860.

Quaife, C. J., Findley, S. D., Erickson, J. C., Froelick, G. J., Kelly, E. J., Zambrowicz, B. P., & Palmiter, R. D. (1994). Induction of a new metallothionein isoform (MT-IV) occurs during differentiation of stratified squamous epithelia. Biochemistry, 33(23), 7250-7259.

Que, E. L., Domaille, D. W., & Chang, C. J. (2008). Metals in neurobiology: probing their chemistry and biology with molecular imaging. Chemical reviews, 108(5), 1517-1549.

Rangarajan, S., & D’Souza, G. A. (2007). Restless legs syndrome in Indian patients having iron deficiency anemia in a tertiary care hospital. Sleep medicine, 8(3), 247-251.

Raymond, M. J., Ray, P., Kaur, G., Fredericks, M., Singh, A. V., & Wan, L. Q. (2017). Multiaxial polarity determines individual cellular and nuclear chirality. Cellular and molecular bioengineering, 10(1), 63-74.

Regland, B., Lehmann, W., Abedini, I., Blennow, K., Jonsson, M., Karlsson, I., ... & Gottfries, C. G. (2001). Treatment of Alzheimer’s disease with clioquinol. Dementia and geriatric cognitive disorders, 12(6), 408-414.

Rinne, J. O., Portin, R., Ruottinen, H., Nurmi, E., Bergman, J., Haaparanta, M., & Solin, O. (2000). Cognitive impairment and the brain dopaminergic system in Parkinson disease:[18F] fluorodopa positron emission tomographic study. Archives of neurology, 57(4), 470-475.

Ritchie, C. W., Bush, A. I., Mackinnon, A., Macfarlane, S., Mastwyk, M., MacGregor, L., ... & Masters, C. L. (2003). Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Aβ amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial. Archives of neurology, 60(12), 1685-1691.

Roberts, B. R., Lim, N. K., McAllum, E. J., Donnelly, P. S., Hare, D. J., Doble, P. A., ... & Crouch, P. J. (2014). Oral treatment with CuII (atsm) increases mutant SOD1 in vivo but protects motor neurons and improves the phenotype of a transgenic mouse model of amyotrophic lateral sclerosis. Journal of Neuroscience, 34(23), 8021-8031.

Roberts, B. R., Tainer, J. A., Getzoff, E. D., Malencik, D. A., Anderson, S. R., Bomben, V. C., ... & Beckman, J. S. (2007). Structural characterization of zinc-deficient human superoxide dismutase and implications for ALS. Journal of molecular biology, 373(4), 877-890.

Rogers, J. T., Randall, J. D., Cahill, C. M., Eder, P. S., Huang, X., Gunshin, H., ... & Gullans, S. R. (2002). An iron-responsive element type II in the 5′-untranslated region of the Alzheimer's amyloid precursor protein transcript. Journal of Biological Chemistry, 277(47), 45518-45528.

Roskams, A. J., & Connor, J. R. (1990). Aluminum access to the brain: a role for transferrin and its receptor. Proceedings of the National Academy of Sciences, 87(22), 9024-9027.

Rossi, M., Ruottinen, H., Soimakallio, S., Elovaara, I., & Dastidar, P. (2013). Clinical MRI for iron detection in Parkinson's disease. Clinical imaging, 37(4), 631-636.

Rowland, L. P., & Shneider, N. A. (2001). Amyotrophic lateral sclerosis. New England Journal of Medicine, 344(22), 1688-1700.

Sabine Becker, J., Matusch, A., Palm, C., Salber, D., Morton, K. A., & Susanne Becker, J. (2010). Bioimaging of metals in brain tissue by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and metallomics. Metallomics, 2(2), 104-111.

Saeed, M., Khan, H., Khan, M. A., Khan, F., Khan, S. A., & Muhammad, N. (2010). Quantification of various metals and cytotoxic profile of aerial parts of Polygonatum verticillatum. Pak. J. Bot, 42(6), 3995-4002.

Saini, N., & Schaffner, W. (2010). Zinc supplement greatly improves the condition of parkin mutant Drosophila. Biological chemistry, 391(5), 513-518.

Salber D, Stoffels G, Pauleit D, Oros-Peusquens AM, Shah NJ, Klauth P, Hamacher K, Coenen HH, Langen KJ (2007) Differential uptake of O-(2-18F-fluoroethyl)-L-tyrosine, L-3H-methionine, and 3H-deoxyglucose in brain abscesses. Journal of Nuclear Medicine 48(12):2056-2062.

Scheiber, I. F., & Dringen, R. (2013). Astrocyte functions in the copper homeostasis of the brain. Neurochemistry international, 62(5), 556-565.

Scheiber, I. F., Mercer, J. F., & Dringen, R. (2014). Metabolism and functions of copper in brain. Progress in neurobiology, 116, 33-57.

Sela, H., Cohen, H., Karpas, Z., & Zeiri, Y. (2017). Distinctive hippocampal zinc distribution patterns following stress exposure in an animal model of PTSD. Metallomics, 9(3), 323-333.

Sensi, S. L., Paoletti, P., Bush, A. I., & Sekler, I. (2009). Zinc in the physiology and pathology of the CNS. Nature reviews neuroscience, 10(11), 780-791.

Sensi, S. L., Rapposelli, I. G., Frazzini, V., & Mascetra, N. (2008). Altered oxidant-mediated intraneuronal zinc mobilization in a triple transgenic mouse model of Alzheimer’s disease. Experimental gerontology, 43(5), 488-492.

Sensi, S. L., Ton-That, D., Sullivan, P. G., Jonas, E. A., Gee, K. R., Kaczmarek, L. K., & Weiss, J. H. (2003). Modulation of mitochondrial function by endogenous Zn2+ pools. Proceedings of the National Academy of Sciences, 100(10), 6157-6162.

Seuma, J., Bunch, J., Cox, A., McLeod, C., Bell, J., & Murray, C. (2008). Combination of immunohistochemistry and laser ablation ICP mass spectrometry for imaging of cancer biomarkers. Proteomics, 8(18), 3775-3784.

Sheykhansari, S., Kozielski, K., Bill, J., Sitti, M., Gemmati, D., Zamboni, P., & Singh, A. V. (2018). Redox metals homeostasis in multiple sclerosis and amyotrophic lateral sclerosis: a review. Cell death & disease, 9(3), 1-16.

Shibata, N. (2001). Transgenic mouse model for familial amyotrophic lateral sclerosis with superoxide dismutase‐1 mutation. Neuropathology, 21(1), 82-92.

Shibata, N., Hirano, A., Yamamoto, T., Kato, Y., & Kobayashi, M. (2000). Superoxide dismutase-1 mutation-related neurotoxicity in familial amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders, 1(3), 143-161.

Shibata, N., Kobayashi, M., Hirano, A., Asayama, K., Horiuchi, S., Dal Canto, M. C., & Gurney, M. E. (1999). Morphological aspects of superoxide dismutase-1 mutation in amyotrophic lateral sclerosis and its transgenic mouse model. Acta histochemica et cytochemica, 32(1), 17-30.

Sian‐Hülsmann, J., Mandel, S., Youdim, M. B., & Riederer, P. (2011). The relevance of iron in the pathogenesis of Parkinson’s disease. Journal of neurochemistry, 118(6), 939-957.

Silvestri, L., & Camaschella, C. (2008). A potential pathogenetic role of iron in Alzheimer's disease. Journal of cellular and molecular medicine, 12(5a), 1548-1550.

Singh, A. V., Subhashree, L., Milani, P., Gemmati, D., & Zamboni, P. (2010). Interplay of iron metallobiology, metalloproteinases, and FXIII, and role of their gene variants in venous leg ulcer. The international journal of lower extremity wounds, 9(4), 166-179.

Smart, T. G., Hosie, A. M., & Miller, P. S. (2004). Zn2+ ions: modulators of excitatory and inhibitory synaptic activity. The Neuroscientist, 10(5), 432-442.

Smith, C. D., Chebrolu, H., Wekstein, D. R., Schmitt, F. A., Jicha, G. A., Cooper, G., & Markesbery, W. R. (2007). Brain structural alterations before mild cognitive impairment. Neurology, 68(16), 1268-1273.

Squitti, R. (2012). Copper dysfunction in Alzheimer's disease: from meta-analysis of biochemical studies to new insight into genetics. Journal of Trace Elements in Medicine and Biology, 26(2-3), 93-96.

Squitti, R., Polimanti, R., Siotto, M., Bucossi, S., Ventriglia, M., Mariani, S., ... & Rossini, P. M. (2013). ATP7B variants as modulators of copper dyshomeostasis in Alzheimer’s disease. Neuromolecular medicine, 15(3), 515-522.

Stöckel, J., Safar, J., Wallace, A. C., Cohen, F. E., & Prusiner, S. B. (1998). Prion protein selectively binds copper (II) ions. Biochemistry, 37(20), 7185-7193.

Sträter, E., Westbeld, A., & Klemm, O. (2010). Pollution in coastal fog at Alto Patache, northern Chile. Environmental Science and Pollution Research, 17(9), 1563-1573.

Strausak, D., Mercer, J. F., Dieter, H. H., Stremmel, W., & Multhaup, G. (2001). Copper in disorders with neurological symptoms: Alzheimer’s, Menkes, and Wilson diseases. Brain research bulletin, 55(2), 175-185.

Strazielle, N., & Ghersi-Egea, J. F. (2013). Physiology of blood–brain interfaces in relation to brain disposition of small compounds and macromolecules. Molecular pharmaceutics, 10(5), 1473-1491.

Sun, X. Y., Wei, Y. P., Xiong, Y., Wang, X. C., Xie, A. J., Wang, X. L., ... & Wang, J. Z. (2012). Synaptic released zinc promotes tau hyperphosphorylation by inhibition of protein phosphatase 2A (PP2A). Journal of Biological Chemistry, 287(14), 11174-11182.

Sussulini, A., & Becker, J. S. (2015). Application of laser microdissection ICP–MS for high resolution elemental mapping in mouse brain tissue: A comparative study with laser ablation ICP–MS. Talanta, 132, 579-582.

Szewczyk, B. (2013). Zinc homeostasis and neurodegenerative disorders. Frontiers in aging neuroscience, 5, 33.

Takeda, A. (2000). Movement of zinc and its functional significance in the brain. Brain research reviews, 34(3), 137-148.

Takeda, A. (2004). Essential trace metals and brain function. JOURNAL-PHARMACEUTICAL SOCIETY OF JAPAN, 124(9), 577-586.

Taylor, E. M., & Morgan, E. H. (1990). Developmental changes in transferrin and iron uptake by the brain in the rat. Developmental Brain Research, 55(1), 35-42.

Tchounwou, P. B., Yedjou, C. G., Patlolla, A. K., & Sutton, D. J. (2012). Heavy metal toxicity and the environment. Molecular, clinical and environmental toxicology, 133-164.

Thakur, A. K., Srivastava, A. K., Srinivas, V., Chary, K. V. R., & Rao, C. M. (2011). Copper alters aggregation behavior of prion protein and induces novel interactions between its N-and C-terminal regions. Journal of Biological Chemistry, 286(44), 38533-38545.

Tokuda, E., & Furukawa, Y. (2016). Copper homeostasis as a therapeutic target in amyotrophic lateral sclerosis with SOD1 mutations. International journal of molecular sciences, 17(5), 636.

Tórsdóttir, G., Kristinsson, J., Sveinbjörnsdóttir, S., Snaedal, J., & Jóhannesson, T. (1999). Copper, ceruloplasmin, superoxide dismutase and iron parameters in Parkinson's disease. Pharmacology & toxicology, 85, 239-243.

Tórsdóttir, G., Kristinsson, J., Sveinbjörnsdóttir, S., Snaedal, J., & Jóhannesson, T. (1999). Copper, ceruloplasmin, superoxide dismutase and iron parameters in Parkinson's disease. Pharmacology & toxicology, 85, 239-243.

Tümer, Z. (2013). An overview and update of ATP7A mutations leading to Menkes disease and occipital horn syndrome. Human mutation, 34(3), 417-429.

Uttara, B., Singh, A. V., Zamboni, P., & Mahajan, R. T. (2009). Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Current neuropharmacology, 7(1), 65-74.

Uversky, V. N., Li, J., & Fink, A. L. (2001). Metal-triggered Structural Transformations, Aggregation, and Fibrillation of Human α-Synuclein: A Possible Molecular Link between Parkinson′ s Disease and Heavy Metal Exposure. Journal of Biological Chemistry, 276(47), 44284-44296.

Valentine JS, Doucette PA, Zittin Potter S (2005) Copper-zinc superoxide dismutase and amyotrophic lateral sclerosis. Annu. Rev. Biochem 74:563-593.

Veasey, S. C., Lear, J., Zhu, Y., Grinspan, J. B., Hare, D. J., Wang, S., ... & Robinson, S. R. (2013). Long-term intermittent hypoxia elevates cobalt levels in the brain and injures white matter in adult mice. Sleep, 36(10), 1471-1481.

Veyrat-Durebex, C., Corcia, P., Mucha, A., Benzimra, S., Mallet, C., Gendrot, C., ... & Blasco, H. (2014). Iron metabolism disturbance in a French cohort of ALS patients. BioMed research international, 2014.

Vickerman, J., & Winograd, N. (2013). Cluster TOF-SIMS imaging and the characterization of biological materials. Cluster Secondary Ion Mass Spectrometry, 269-312.

Visconti, A., Cotichini, R., Cannoni, S., Bocca, B., Forte, G., Ghazaryan, A., ... & Ristori, G. (2005). Concentration of elements in serum of patients affected by multiple sclerosis with first demyelinating episode: a six-month longitudinal follow-up study. Annali dell'Istituto superiore di sanita, 41(2), 217-222.

Vulpe, C., Levinson, B., Whitney, S., Packman, S., & Gitschier, J. (1993). Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper–transporting ATPase. Nature genetics, 3(1), 7-13.

Waggoner, D. J., Bartnikas, T. B., & Gitlin, J. D. (1999). The role of copper in neurodegenerative disease. Neurobiology of disease, 6(4), 221-230.

Wallis, L. I., Paley, M. N., Graham, J. M., Grünewald, R. A., Wignall, E. L., Joy, H. M., & Griffiths, P. D. (2008). MRI assessment of basal ganglia iron deposition in Parkinson's disease. Journal of Magnetic Resonance Imaging: An Official Journal of the International Society for Magnetic Resonance in Medicine, 28(5), 1061-1067.

Walter, E. D., Stevens, D. J., Spevacek, A. R., Visconte, M. P., Rossi, A. D., & Millhauser, G. L. (2009). Copper binding extrinsic to the octarepeat region in the prion protein. Current Protein and Peptide Science, 10(5), 529-535.

Wan, L., Nie, G., Zhang, J., Luo, Y., Zhang, P., Zhang, Z., & Zhao, B. (2011). β-Amyloid peptide increases levels of iron content and oxidative stress in human cell and Caenorhabditis elegans models of Alzheimer disease. Free Radical Biology and Medicine, 50(1), 122-129.

Wang, J., Zhang, Y., Tang, L., Zhang, N., & Fan, D. (2011). Protective effects of resveratrol through the up-regulation of SIRT1 expression in the mutant hSOD1-G93A-bearing motor neuron-like cell culture model of amyotrophic lateral sclerosis. Neuroscience letters, 503(3), 250-255.

Wang, L. M., Becker, J. S., Wu, Q., Oliveira, M. F., Bozza, F. A., Schwager, A. L., ... & Morton, K. A. (2010). Bioimaging of copper alterations in the aging mouse brain by autoradiography, laser ablation inductively coupled plasma mass spectrometry and immunohistochemistry. Metallomics, 2(5), 348-353.

Wang, X. S., Lee, S., Simmons, Z., Boyer, P., Scott, K., Liu, W., & Connor, J. (2004). Increased incidence of the Hfe mutation in amyotrophic lateral sclerosis and related cellular consequences. Journal of the neurological sciences, 227(1), 27-33.

Wang, X., Moualla, D., Wright, J. A., & Brown, D. R. (2010). Copper binding regulates intracellular alpha‐synuclein localisation, aggregation and toxicity. Journal of neurochemistry, 113(3), 704-714.

Ward, R. J., Zucca, F. A., Duyn, J. H., Crichton, R. R., & Zecca, L. (2014). The role of iron in brain ageing and neurodegenerative disorders. The Lancet Neurology, 13(10), 1045-1060.

Weinreb, O., Amit, T., Mandel, S., Kupershmidt, L., & Youdim, M. B. (2010). Neuroprotective multifunctional iron chelators: from redox-sensitive process to novel therapeutic opportunities. Antioxidants & redox signaling, 13(6), 919-949.

Weiskirchen, S., Kim, P., & Weiskirchen, R. (2019). Laser Ablation Inductively Coupled Plasma Spectrometry: Metal Imaging in Experimental and Clinical Wilson Disease. Inorganics, 7(4), 54.

Wijesekera, L. C., & Leigh, P. N. (2009). Amyotrophic lateral sclerosis. Orphanet journal of rare diseases, 4(1), 1-22.

Wilms, H., Rosenstiel, P., Sievers, J., Deuschl, G., Zecca, L., & Lucius, R. (2003). Activation of microglia by human neuromelanin is NF‐κB‐dependent and involves p38 mitogen‐activated protein kinase: implications for Parkinson's disease. The FASEB journal, 17(3), 1-20.

Wilquet, V., & De Strooper, B. (2004). Amyloid-beta precursor protein processing in neurodegeneration. Current opinion in neurobiology, 14(5), 582-588.

Wind, M., Feldmann, I., Jakubowski, N., & Lehmann, W. D. (2003). Spotting and quantification of phosphoproteins purified by gel electrophoresis and laser ablation‐element mass spectrometry with phosphorus‐31 detection. Electrophoresis, 24(7‐8), 1276-1280.

Winkler, E. A., Sengillo, J. D., Sagare, A. P., Zhao, Z., Ma, Q., Zuniga, E., ... & Zlokovic, B. V. (2014). Blood–spinal cord barrier disruption contributes to early motor-neuron degeneration in ALS-model mice. Proceedings of the National Academy of Sciences, 111(11), E1035-E1042.

Wong, C. P., Magnusson, K. R., & Ho, E. (2013). Increased inflammatory response in aged mice is associated with age-related zinc deficiency and zinc transporter dysregulation. The Journal of nutritional biochemistry, 24(1), 353-359.

Wright, J. A., Wang, X., & Brown, D. R. (2009). Unique copper‐induced oligomers mediate alpha‐synuclein toxicity. The FASEB Journal, 23(8), 2384-2393.

Wu, B., Niehren, S., & Becker, J. S. (2011). Mass spectrometric imaging of elements in biological tissues by new BrainMet technique—laser microdissection inductively coupled plasma mass spectrometry (LMD-ICP-MS). Journal of analytical atomic spectrometry, 26(8), 1653-1659.

Xu, N., Majidi, V., Ehmann, W. D., & Markesbery, W. R. (1992). Determination of aluminium in human brain tissue by electrothermal atomic absorption spectrometry. Journal of Analytical Atomic Spectrometry, 7(5), 749-751.

Yager, J. Y., & Hartfield, D. S. (2002). Neurologic manifestations of iron deficiency in childhood. Pediatric neurology, 27(2), 85-92.

Yamamoto, A., Shin, R. W., Hasegawa, K., Naiki, H., Sato, H., Yoshimasu, F., & Kitamoto, T. (2002). Iron (III) induces aggregation of hyperphosphorylated τ and its reduction to iron (II) reverses the aggregation: implications in the formation of neurofibrillary tangles of Alzheimer's disease. Journal of neurochemistry, 82(5), 1137-1147.

Yasui, M., Ota, K., & Garruto, R. M. (1993). Concentrations of zinc and iron in the brains of Guamanian patients with amyotrophic lateral sclerosis and parkinsonism-dementia. Neurotoxicology, 14(4), 445-450.

Yegambaram, M., Manivannan, B., G Beach, T., & U Halden, R. (2015). Role of environmental contaminants in the etiology of Alzheimer’s disease: a review. Current Alzheimer Research, 12(2), 116-146.

Yoshida, M., Takahashi, Y., Koike, A., Fukuda, Y., Goto, J., & Tsuji, S. (2010). A mutation database for amyotrophic lateral sclerosis. Human mutation, 31(9), 1003-1010.

Youdim, M. B. (1990). Neuropharmacological and neurobiochemical aspects of iron deficiency. In Brain, behaviour, and iron in the infant diet (pp. 83-99). Springer, London.

Yu, W. H., Lukiw, W. J., Bergeron, C., Niznik, H. B., & Fraser, P. E. (2001). Metallothionein III is reduced in Alzheimer’s disease. Brain research, 894(1), 37-45.

Zamboni, P., Tognazzo, S., Izzo, M., Pancaldi, F., Scapoli, G. L., Liboni, A., & Gemmati, D. (2005). Hemochromatosis C282Y gene mutation increases the risk of venous leg ulceration. Journal of vascular surgery, 42(2), 309-314.

Zecca, L., Fariello, R., Riederer, P., Sulzer, D., Gatti, A., & Tampellini, D. (2002). The absolute concentration of nigral neuromelanin, assayed by a new sensitive method, increases throughout the life and is dramatically decreased in Parkinson's disease. FEBS letters, 510(3), 216-220.

Zecca, L., Shima, T., Stroppolo, A., Goj, C., Battiston, G. A., Gerbasi, R., ... & Swartz, H. M. (1996). Interaction of neuromelanin and iron in substantia nigra and other areas of human brain. Neuroscience, 73(2), 407-415.

Zecca, L., Youdim, M. B., Riederer, P., Connor, J. R., & Crichton, R. R. (2004). Iron, brain ageing and neurodegenerative disorders. Nature Reviews Neuroscience, 5(11), 863-873.

Zheng, W., & Monnot, A. D. (2012). Regulation of brain iron and copper homeostasis by brain barrier systems: implication in neurodegenerative diseases. Pharmacology & therapeutics, 133(2), 177-188.

Zoriy, M. V., Dehnhardt, M., Reifenberger, G., Zilles, K., & Becker, J. S. (2006). Imaging of Cu, Zn, Pb and U in human brain tumor resections by laser ablation inductively coupled plasma mass spectrometry. International Journal of Mass Spectrometry, 257(1-3), 27-33.

Zoriy, M., Matusch, A., Spruss, T., & Becker, J. S. (2007). Laser ablation inductively coupled plasma mass spectrometry for imaging of copper, zinc, and platinum in thin sections of a kidney from a mouse treated with cis-platin. International Journal of Mass Spectrometry, 260(2-3), 102-106.

Zucca, F. A., Basso, E., Cupaioli, F. A., Ferrari, E., Sulzer, D., Casella, L., & Zecca, L. (2014). Neuromelanin of the human substantia nigra: an update. Neurotoxicity research, 25(1), 13-23.

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