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Issue 19, 2014

Biological metals and metal-targeting compounds in major neurodegenerative diseases

Author affiliations

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

Article information


Submitted
28 Apr 2014
First published
07 Aug 2014

This article is Open Access

Chem. Soc. Rev., 2014,43, 6727-6749
Article type
Review Article
Author version available

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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