Metal Ions in Neurological Systems

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These findings are related to decreased lysyl oxidase activity, which leads to disruption of collagen and elastin cross-linking. The autonomic nervous system is involuntary and plays a crucial role in the maintenance of homeostasis through innervation of cardiac muscle, smooth muscle, and endocrine and exocrine glands The autonomic nervous system has 2 divisions: the sympathetic and the parasympathetic systems. Both are tonically active, and the frequency of discharge of neurons in both systems can increase or decrease.

With diminished production of norepinephrine, there is impaired innervation of postganglionic sympathetic targets. This may produce bradycardia, orthostatic hypotension, and chronic diarrhea in persons with occipital horn syndrome 23 — The overall biochemical phenotype low serum copper and ceruloplasmin and abnormal plasma and cerebrospinal fluid catecholamine concentrations is similar to that seen in Menkes disease, although often less severe.

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Parkinson disease is a common neurodegenerative movement disorder characterized by impaired motor function, including resting tremors, rigidity, bradykinesia, and postural instability Copper is the most effective in accelerating aggregation, suggesting a possible link between abnormal copper homoeostasis and this condition The prion diseases are a group of neurodegenerative diseases that affect the gray matter of the central nervous system and produce neuronal loss, gliosis, and spongiform degeneration 29 , Prion diseases are caused by prion proteins PrPs that have been modified such that they fold improperly.

PrPs are highly expressed in the central nervous system and contain high-affinity copper-binding sites in their amino-terminal regions. In vitro, copper enhances renaturation and stabilization of PrPs, enhancing protease resistance and infectivity, and leading to speculation about copper's role in the pathogenesis of prion diseases 6 , Wilson disease is an autosomal recessive disorder caused by the loss-of-function mutations in the copper transport gene ATP7B 1.

This results in hepatic cirrhosis and progressive basal ganglia degeneration in the brain The loss of ATP7B results in production of apoceruloplasmin, which is rapidly degraded in the plasma, resulting in reduced copper-carrying capacity. There is concomitant impairment in excretion of copper into bile. This leads to hepatic copper accumulation and damage, elevated levels of non-ceruloplasmin-bound copper in the plasma and, ultimately, copper overload in extrahepatic tissues 31 , Copper accumulation in the basal ganglia leads to Parkinsonian symptoms, including tremors and dystonia.

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Indeed, Wilson disease may properly be classified as a movement disorder. In addition to liver and brain, the eye is also a primary site of copper deposition in Wilson disease.

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Metal ions in the brain are a necessity as well as a poison. The presence of metal ions in the active sites of biological catalysts or metalloproteins and in the biological functioning of nucleic acids is very well documented and they are required for brain activity. Editorial Reviews. From the Back Cover. Metal ions in the brain are a necessity as well as a Metal Ions in Neurological Systems Edition, Kindle Edition.

A pathognomonic sign, the Kayser-Fleischer KF ring, is an annular deposition of copper in the periphery of the cornea. Oral copper chelating agents are effective in restoring copper homeostasis in many patients with Wilson disease 31 , If reliable biomarkers of total-body copper status were available, potentially undesirable health effects due to excess or deficiency of this trace metal could be prevented.

Several biomarkers can be considered to screen for copper deficiency. In copper deficiency, DBH activity may decrease and result in elevated ratios of dopamine to norepinephrine, as seen in Menkes disease Impaired activity of DBH also leads to increased urinary ratios of homovanillic acid to vanillylmandelic acid Other cuproenzymes may also be measureable as potential biomarkers of copper deficiency.

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We also note several potential biomarkers of copper excess. Excess copper is deposited in the liver where high levels can cause injury.


Interleukin-2 may also be useful as a biomarker of copper excess; concentrations of interleukin-2 increase in response to copper supplementation Recent evidence highlights the important role of copper in the development and maintenance of the mammalian nervous system. Further advances in understanding these functions will affect our understanding of the human neurological disorders reviewed here and hopefully will suggest useful therapeutic approaches.

The biochemical phenotypes associated with some of these disorders suggest potential for detection of copper excess and deficiency in the general population.

Evaluation of the utility of such biomarkers awaits formal population surveys. The contributions of the authors were as follows—VD prepared serial drafts of the manuscript and SGK edited the drafts and delivered the symposium presentation. The authors had no conflicts of interest to report. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide.

Sign In or Create an Account. Sign In. Advanced Search. The role of metal ions in dopaminergic neuron degeneration in Parkinsonism and Parkinsons disease. Iron cysteine and neurodegeneration during Parkinsons disease. Copper uptake and trafficking in the brain. Prion diseases and manganism.

The Chemistry of Metals in Biological Systems

Metal ions and beta amyloid conformational modifications and biological aspects. Betaamyloid toxicity increases with hydrophobicity in the presence of metal ions. Oxidative stress in neurodegeneration targeting mitochondria as a therapeutic aid.

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More detailed descriptions of particular targeting strategies are discussed in later sections. Understanding the relationships between ion channel structure and function may provide insight into the causes and potential treatments for these genetic disorders. Metal ions and beta amyloid conformational modifications and biological aspects. Fura-2, loaded into J Achieving a spatial resoln. Preliminary biol. Another class of proteins involved in metalloneurochemistry are the metallothioneins

The chemical mechanism of oxidative stress by copperII and ironIII ions in several neurodegenerative disorders. Metal ion roles and responses in the CNS under toxic organophosphonate exposure traces of understanding and various open questions.

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Fish depend on an intact nervous system, including their sense organs, for mediating relevant behaviour such as food search, predator recognition, communication and orientation. Unfortunately, the nervous system is most vulnerable and injuries to its elements may dramatically change the behaviour and consequently the survival of fish. Heavy metals are well known pollutants in the aquatic environment.

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Their interaction with relevant chemical stimuli may interfere with the communication between fish and environment. The affinity for a number of ligands and macromolecules makes heavy metals most potent neurotoxins.