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Biological metals and metal-targeting compounds in major neurodegenerative diseases.
Chem Soc Rev. 2014 Oct 07; 43(19):6727-49.CS

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.

Authors+Show Affiliations

Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, 3010, Australia.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

25099276

Citation

Barnham, Kevin J., and Ashley I. Bush. "Biological Metals and Metal-targeting Compounds in Major Neurodegenerative Diseases." Chemical Society Reviews, vol. 43, no. 19, 2014, pp. 6727-49.
Barnham KJ, Bush AI. Biological metals and metal-targeting compounds in major neurodegenerative diseases. Chem Soc Rev. 2014;43(19):6727-49.
Barnham, K. J., & Bush, A. I. (2014). Biological metals and metal-targeting compounds in major neurodegenerative diseases. Chemical Society Reviews, 43(19), 6727-49. https://doi.org/10.1039/c4cs00138a
Barnham KJ, Bush AI. Biological Metals and Metal-targeting Compounds in Major Neurodegenerative Diseases. Chem Soc Rev. 2014 Oct 7;43(19):6727-49. PubMed PMID: 25099276.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Biological metals and metal-targeting compounds in major neurodegenerative diseases. AU - Barnham,Kevin J, AU - Bush,Ashley I, Y1 - 2014/08/07/ PY - 2014/8/8/entrez PY - 2014/8/8/pubmed PY - 2015/5/15/medline SP - 6727 EP - 49 JF - Chemical Society reviews JO - Chem Soc Rev VL - 43 IS - 19 N2 - 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. SN - 1460-4744 UR - https://www.unboundmedicine.com/medline/citation/25099276/Biological_metals_and_metal_targeting_compounds_in_major_neurodegenerative_diseases_ L2 - https://doi.org/10.1039/c4cs00138a DB - PRIME DP - Unbound Medicine ER -