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Issue 19, 2014
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Biological metals and metal-targeting compounds in major neurodegenerative diseases

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Abstract

Multiple abnormalities occur in the homeostasis of essential endogenous brain biometals in age-related neurodegenerative disorders, Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. As a result, metals both accumulate in microscopic proteinopathies, and can be deficient in cells or cellular compartments. Therefore, bulk measurement of metal content in brain tissue samples reveal only the “tip of the iceberg”, with most of the important changes occurring on a microscopic and biochemical level. Each of the major proteins implicated in these disorders interacts with biological transition metals. Tau and the amyloid protein precursor have important roles in normal neuronal iron homeostasis. Changes in metal distribution, cellular deficiencies, or sequestration in proteinopathies all present abnormalities that can be corrected in animal models by small molecules. These biochemical targets are more complex than the simple excess of metals that are targeted by chelators. In this review we illustrate some of the richness in the science that has developed in the study of metals in neurodegeneration, and explore its novel pharmacology.

Graphical abstract: Biological metals and metal-targeting compounds in major neurodegenerative diseases

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Publication details

The article was received on 28 Apr 2014 and first published on 07 Aug 2014


Article type: Review Article
DOI: 10.1039/C4CS00138A
Citation: Chem. Soc. Rev., 2014,43, 6727-6749
  • Open access: Creative Commons BY-NC license
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    Biological metals and metal-targeting compounds in major neurodegenerative diseases

    K. J. Barnham and A. I. Bush, Chem. Soc. Rev., 2014, 43, 6727
    DOI: 10.1039/C4CS00138A

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