Skip to main content

Advertisement

Log in

Roles of Metal Microelements in Neurodegenerative Diseases

  • REVIEWS
  • Published:
Neurophysiology Aims and scope

Neurodegenerative diseases are characterized by a progressive loss of neuronal structures and functions. Although all biochemical and/or physiological processes are not completely understood, it is known that the main neurodegenerative diseases, like Alzheimer’s, Parkinson’s, Huntington’s, and prion diseases, and also amyotrophic lateral sclerosis (ALS) present certain obvious similarities. Biometal microelements, such as copper, iron, manganese, and zinc, are crucial for many physiological functions, especially in the CNS. Shifts in the amounts of these metals are essential for the development and maintenance of numerous enzymatic activities, mitochondrial functions, neurotransmission, and also for memorization and learning. However, with deregulations in their homeostasis, particularly in those connected with redox activity, there are consequent changes in the ion and microelement balance. This redox activity may contribute to the production of free radicals that can react with various organic substrates, thus generating increased levels of oxidative stress. There is growing evidence that metal microelements play significant roles in the pathogenesis of neurodegenerative diseases. The interaction between metals and CNS proteins is crucial in the development or absence of neurodegeneration. In this way, homeostasis of metal microelements represents a mechanism of extreme importance. Our paper aims at an updated and critical review of the role of the respective metals in neurodegenerative diseases and the main related pathogenic mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. M. F. C. Leal, R. I. L. Catarino, A. M. Pimenta, et al., “Lead migration from toys by anodic stripping voltammetry using a bismuth film electrode,” Arch. Environ. Occup. Health,71, No. 5, 300–306 (2016).

    CAS  PubMed  Google Scholar 

  2. K. J. Barnham and A. I. Bush, “Metals in Alzheimer’s and Parkinson’s diseases,” Curr. Opin. Chem. Biol.,12, No. 2, 222–228 (2008).

    CAS  PubMed  Google Scholar 

  3. M. F. C. Leal, R. I. L. Catarino, A. M. Pimenta, et al., “Speciation of copper and zinc in urine – importance of metals in neurodegenerative diseases,” Quim. Nova,35, No. 10, 1985–1990 (2012).

    CAS  Google Scholar 

  4. A. Rauk, “The chemistry of Alzheimer`s disease,” Chem. Soc. Rev.,38, No. 9, 2698–2715 (2009).

    CAS  PubMed  Google Scholar 

  5. P. Zatta, D. Drago, S. Bolognin, and S. L. Sensi, “Alzheimer’s disease, metal ions and metal homeostatic therapy,” Trends Pharmacol. Sci.,30, No. 7, 346–355 (2009).

    CAS  PubMed  Google Scholar 

  6. F. Sola Vigo, G. Kedikian, L. Heredia, et al., “Amyloidprecursor protein mediates neuronal toxicity of amyloid β through Go protein activation,” Neurobiol. Aging,30, No. 9, 1379–1392 (2009).

    CAS  PubMed  Google Scholar 

  7. G. Silvestrelli, A. Lanari, L. Parnetti, and F. Amenta, “Treatment of Alzheimer’s disease: From pharmacology to a better understanding of disease pathophysiology,” Mech. Ageing Dev.,127, No. 2, 148–157 (2006).

    CAS  PubMed  Google Scholar 

  8. R. B. Maccioni, G. Farías, I. Morales, and R. Navarrete, “The revitalized tau hypothesis on Alzheimer’s disease,” Arch. Med. Res.,41, No. 3, 226–231 (2010).

    CAS  PubMed  Google Scholar 

  9. H. A. G. Teive, “Etiopathogenesis of Parkinson disease,” Rev. Neurociências,13, No. 4, 201–214 (2005).

    Google Scholar 

  10. D. Weintraub, C. L. Comella, and S. Horn, “Parkinson’s disease – Part I: Pathophysiology, symptoms, burden, diagnosis, and assessment,” Am. J. Manag. Care,14, Suppl. 2, S40–S48 (2008).

    PubMed  Google Scholar 

  11. T. Togo, E. Iseki, W. Marui, et al., “Glial involvement in the degeneration process of Lewy body-bearing neurons and the degradation process of Lewy bodies in brains of dementia with Lewy bodies,” J. Neurol. Sci.,184, No. 1, 71–75 (2001).

    CAS  PubMed  Google Scholar 

  12. F. Walker,” Huntington’s disease,” Lancet,369, No. 9557, 218–228 (2007).

  13. L. A. Raymond, V. M. André, C. Cepeda, et al., “Pathophysiology of Huntington’s disease: timedependent alterations in synaptic and receptor function,” Neuroscience,198, 252–273 (2011).

    CAS  PubMed  Google Scholar 

  14. U. Jones, M. Busse, S. Enright, and A. E. Rosser, “Respiratory decline is integral to disease progression in Hunting- ton’s disease,” Eur. Respir. J.,48, No. 2, 585–588 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. P. Maiti, J. Manna, S. Veleri, and S. Frautschy, “Molecular chaperone dysfunction in neurodegenerative diseases and effects of curcumin,” BioMed Res. Int.,2014, 495091 (2014).

    PubMed  PubMed Central  Google Scholar 

  16. Y. Hayashi, K. Homma, and H. Ichijo, “SOD1 in neurotoxicity and its controversial roles in SOD1 mutation-negative ALS,” Adv. Biol. Regul.,60, 95–104 (2016).

    CAS  PubMed  Google Scholar 

  17. M. T. Carrì, N. D’Ambrosi, and M. Cozzolino, “Pathways to mitochondrial dysfunction in ALS pathogenesis,” Biochem. Biophys. Res. Commun.,483, No. 4, 1187–1193 (2017).

    PubMed  Google Scholar 

  18. I. Keskin, E. Forsgren, D. J. Lange, et al., “Effects of cellular pathway disturbances on misfolded superoxide dismutase-1 in fibroblasts derived from ALS patients,” PLoS One,11, No. 2, e0150133 (2016).

    PubMed  PubMed Central  Google Scholar 

  19. M. Manix, P. Kalakoti, M. Henry, et al., “Creutzfeldt-Jakob disease: updated diagnostic criteria, treatment algorithm, and the utility of brain biopsy,” Neurosurg. Focus,39, No. 5, E2 (2015).

    PubMed  Google Scholar 

  20. C. Chen and X. P. Dong, “Epidemiological characteristics of human prion diseases,” Infect. Dis. Poverty,5, No. 1, 47 (2016).

    PubMed  PubMed Central  Google Scholar 

  21. S. Venneti, “Prion diseases,” Clin. Lab. Med.,30, No. 1, 293–309 (2010).

    PubMed  Google Scholar 

  22. A. V. Menon, J. Chang, and J. Kim, “Mechanisms of divalent metal toxicity in affective disorders,” Toxicology,339, 58–72 (2016).

    CAS  PubMed  Google Scholar 

  23. I. F. Scheiber, J. F. B. Mercer, and R. Dringen, “Metabolism and functions of copper in brain,” Prog. Neurobiol.,116, 33–57 (2014).

    CAS  PubMed  Google Scholar 

  24. M. F. C. Leal and C. M. G. van den Berg, “Evidence for strong copper(I) complexation by organic ligands in seawater,” Aquat. Geochem.,4, 49–75 (1998).

    CAS  Google Scholar 

  25. M. F. C. Leal, M. T. S. D. Vasconcelos, and C. M. G. van den Berg, “Copper-induced release of complexing ligands similar to thiols by Emiliania huxleyi in seawater cultures,” Limnol. Oceanogr.,44, No. 7, 1750–1762 (1999).

    CAS  Google Scholar 

  26. T. Marino, N. Russo, M. Toscano, and M. Pavelka, “On the metal ion (Zn2+, Cu2+) coordination with betaamyloid peptide: DFT computational study,” Interdiscip. Sci. Comput. Life Sci.,2, No. 1, 57–69 (2010).

    CAS  Google Scholar 

  27. J. H. Fox, J. A. Kama, G. Lieberman, et al., “mechanisms of copper ion mediated Huntington’s disease progression,” PLoS One,2, No. 3, e334 (2007).

    PubMed  PubMed Central  Google Scholar 

  28. S. Rivera-Mancía, I. Pérez-Neri, C. Ríos, et al., “The transition metals copper and iron in neurodegenerative diseases,” Chem. Biol. Interact.,186, No. 2, 184–199 (2010).

    PubMed  Google Scholar 

  29. D. B. Lovejoy and G. J. Guillemin, “The potential for the transition metal-mediated neurodegeneration in amyotrophic lateral sclerosis,” Front. Aging Neurosci.,6, 173 (2014).

    PubMed  PubMed Central  Google Scholar 

  30. D. R. Brown, “Copper and prion diseases,” Biochem. Soc. Trans.,30, No. 4, 742–745 (2002).

    CAS  PubMed  Google Scholar 

  31. H. Kozlowski, A. Janicka-Klos, J. Brasun, et al., “Copper, iron, and zinc ions homeostasis and their role in neurodegenerative disorders (metal uptake, transport, distribution and regulation),” Coord. Chem. Rev.,253, Nos. 21–22, 2665–2685 (2009).

    CAS  Google Scholar 

  32. A. Singh, A. O. Isaac, X. Luo, et al., “Abnormal brain iron homeostasis in human and animal prion disorders,” PLoS Pathog.,5, No. 3, e1000336 (2009).

    PubMed  PubMed Central  Google Scholar 

  33. H. Zheng, M. B. Youdim, and M. Fridkin, “Site-activated chelators targeting acetylcholinesterase and monoamine oxidase for Alzheimer’s therapy,” ACS Chem. Biol.,5, No. 6, 603–610 (2010).

    CAS  PubMed  Google Scholar 

  34. J. A. Duce and A. I. Bush, “Biological metals and Alzheimer’s disease: Implications for therapeutics and diagnostics,” Prog. Neurobiol.,92, No.1, 1–18 (2010).

    CAS  PubMed  Google Scholar 

  35. L. L. Fernandez, L. H. T. Fornari, M. Viter, and N. Schroder, “Iron and neurodegeneration,” Sci. Med.,17, No. 4, 218–224 (2007).

    Google Scholar 

  36. N. P. Mena, P. J. Urrutia, F. Lourido, et al., “Mitochondrial iron homeostasis and its dysfunctions in neurodegenerative disorders,” Mitochondrion,21, 92–105 (2015).

    CAS  PubMed  Google Scholar 

  37. M. Hadzhieva, E. Kirches, and C. Mawrin, “Review: Iron metabolism and the role of iron in neurodegenerative disorders,” Neuropathol. Appl. Neurobiol.,40, No. 3, 240–257 (2014).

    CAS  PubMed  Google Scholar 

  38. M. Farina, D. S. Avila, J. B. da Rocha, and M. Aschner, “Metals, oxidative stress and neurodegeneration: A focus on iron, manganese and mercury,” Neurochem. Int.,62, No. 5, 575–594 (2013).

    CAS  PubMed  Google Scholar 

  39. K. J. Horning, S. W. Caito, K. G. Tipps, et al., “Manganese is essential for neuronal health,” Annu. Rev. Nutr.,35, 71–108 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. J. L. Madison, M. Wegrzynowicz, M. Aschner, and A. B. Bowman, “Disease-toxicant interactions in manganese exposed Huntington disease mice: Early changes in striatal neuron morphology and dopamine metabolism,” PLoS One,7, No. 2, e31024 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. D. R. Brown, “Neurodegeneration and oxidative stress: prion disease results from loss of antioxidant defence,” Folia Neuropathol.,43, No. 4, 229–243 (2005).

    CAS  PubMed  Google Scholar 

  42. M. T. S. D. Vasconcelos and M. F. C. Leal, “Antagonistic interactions of Pb and Cd on Cu uptake, growth inhibition and chelator release in the marine algae Emiliania huxleyi,” Mar. Chem.,75, Nos. 1–2, 123–139 (2001).

    CAS  Google Scholar 

  43. L. Strużyńska, “A glutamatergic component of lead toxicity in adult brain: The role of astrocytic glutamate transporters,” Neurochem. Int.,55, Nos. 1–3, 151–156 (2009).

    PubMed  Google Scholar 

  44. L. D. White, D. A. Cory-Slechta, M. E. Gilbert, et al., “New and evolving concepts in the neurotoxicology of lead,” Toxicol. Appl. Pharmacol.,225, No. 1, 1–27 (2007).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. F. C. Leal.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Leal, M.F.C., Catarino, R.I.L., Pimenta, A.M. et al. Roles of Metal Microelements in Neurodegenerative Diseases. Neurophysiology 52, 80–88 (2020). https://doi.org/10.1007/s11062-020-09854-5

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11062-020-09854-5

Keywords

Navigation