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Role of copper in human neurological disorders 1-3

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Abstract

Copper is a trace element present in all tissues and is required for cellular respiration, peptide amidation, neurotransmitter biosynthe-sis, pigment formation, and connective tissue strength.

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Role of copper in human neurological disorders
Tâm Trương

The American Journal of Clinical Nutrition, 2008

Copper is a trace element present in all tissues and is required for cellular respiration, peptide amidation, neurotransmitter biosynthesis, pigment formation, and connective tissue strength. Copper is a cofactor for numerous enzymes and plays an important role in central nervous system development; low concentrations of copper may result in incomplete development, whereas excess copper maybe injurious. Copper may be involved in free radical production, via the Haber-Weiss reaction, that results in mitochondrial damage, DNA breakage, and neuronal injury. Evidence of abnormal copper transport and aberrant copper-protein interactions in numerous human neurological disorders supports the critical importance of this trace metal for proper neurodevelopment and neurological function. The biochemical phenotypes of human disorders that involve copper homeostasis suggest possible biomarkers of copper status that may be applicable to general populations.

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Is there a role for copper in neurodegenerative diseases?
Ariel Reyes

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Copper is an essential metal in living organisms; thus, the maintenance of adequate copper levels is of vital importance and is highly regulated. Dysfunction of copper metabolism leading to its excess or deficiency results in severe ailments. Two examples of illnesses related to alterations in copper metabolism are Menkes and Wilson diseases. Several proteins are involved in the maintenance of copper homeostasis, including copper transporters and metal chaperones. In the last several years, the b-amyloid-precursor protein (b-APP) and the prion protein (PrP C ), which are related to the neurodegenerative disorders Alzheimer and prion diseases respectively, have been associated with copper metabolism. Both proteins bind copper through copper-binding domains that also have been shown to reduce copper in vitro. Moreover, this ability to reduce copper is associated with a neuroprotective effect exerted by the copper-binding domain of both proteins against copper in vivo. In addition to a functional link between copper and b-APP or PrP C , evidence suggests that copper has a role in Alzheimer and prion diseases. Here, we review the evidence that supports both, the role of b-APP and PrP C , in copper metabolism and the putative role of copper in neurodegenerative diseases.

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Copper uptake and trafficking in the brain
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The aim of this chapter is to give a general view on the current status of the scientific basis for the role of copper in human health and disease, outlining the roles of copper in human metabolism and bioenergetics, its coordination chemistry as well as the biological ligands involved in the multiple steps of metal incorporation. In particular, our attention has been focused towards the interaction of copper status and brain function in health and disease, with particular consideration to the role of copper in the pathogenesis of Wilson's, of Menkes, and of human neurodegenerative diseases. Data on interactions between essential trace elements and copper, from the level of absorption in the gut to other systems in the body, are also presented. Particular attention is paid to copper-dependent enzymes in the central nervous system and to copper uptake and trafficking in brain cells.

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Copper is one of the most abundant basic transition metals in the human body. It takes part in oxygen metabolism, collagen synthesis, and skin pigmentation, maintaining the integrity of blood vessels, as well as in iron homeostasis, antioxidant defense, and neurotransmitter synthesis. It may also be involved in cell signaling and may participate in modulation of membrane receptor-ligand interactions, control of kinase and related phosphatase functions, as well as many cellular pathways. Its role is also important in controlling gene expression in the nucleus. In the nervous system in particular, copper is involved in myelination, and by modulating synaptic activity as well as excitotoxic cell death and signaling cascades induced by neurotrophic factors, copper is important for various neuronal functions. Current data suggest that both excess copper levels and copper deficiency can be harmful, and careful homeostatic control is important. This knowledge opens up an important new area...

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Copper status abnormalities and how to measure them in neurodegenerative disorders
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Copper is essential for life. It plays a pivotal role in the central nervous system, in which a low concentration of copper results in incomplete development, whereas an excess of copper is injurious. Redox reactions are at the basis of copper toxicity: in fact, it catalyses the production of reactive oxygen species in Fenton or Haber-Weiss reactions. Abnormalities of copper homeostasis in neurodegenerative disorders were discovered decades ago. The steady increase in reports from the literature demonstrating copper involvement in neurodegenerative disorders coincides with the improvement, reliability and low cost devices which measure copper markers in biological samples. These devices also demonstrate increasing relevance in diagnosis and in therapy monitoring as well. Methods and new perspectives for the analysis of copper markers status are discussed herein, weighing pros and cons of application to a specific neurological disorder. In particular, it have been introduced three pa...

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