Biological metals and Alzheimer's disease: Implications for therapeutics and diagnostics

Duce, James A.; Bush, Ashley I.

doi:10.1016/j.pneurobio.2010.04.003

Cited by 260 publications

(188 citation statements)

References 319 publications

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“…It is possible that, in the future, new drugs could be developed that specifically target this A␤ redox activity, and these could be beneficial even in the more advanced stages of AD. Metal ion chelators are already in development as a possible AD therapy (61), but drugs that specifically bind to sites in A␤ fibrils that are involved in this redox activity could be a viable alternative option.…”

Section: Discussionmentioning

confidence: 99%

β-Amyloid Fibrils in Alzheimer Disease Are Not Inert When Bound to Copper Ions but Can Degrade Hydrogen Peroxide and Generate Reactive Oxygen Species

Mayes

Tinker-Mill

Kolosov

et al. 2014

Journal of Biological Chemistry

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Background: Metal-associated ␤-amyloid (A␤) aggregates are implicated in the pathogenesis of Alzheimer disease. Results: Copper bound A␤(1-42) aggregates, including fibrils, degrade hydrogen peroxide, forming hydroxyl radicals and carbonyls. Conclusion: Copper-bound A␤ fibrils can retain redox activity. Significance: A␤ fibrils bound to copper are not inert end points and may be a source of oxidative stress in the Alzheimer brain.

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Section: Discussionmentioning

confidence: 99%

β-Amyloid Fibrils in Alzheimer Disease Are Not Inert When Bound to Copper Ions but Can Degrade Hydrogen Peroxide and Generate Reactive Oxygen Species

Mayes

Tinker-Mill

Kolosov

et al. 2014

Journal of Biological Chemistry

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“…Metal coordination properties of Ab have been investigated employing a wide range of techniques such as nuclear magnetic resonance (NMR) spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, circular dichroism (CD) spectroscopy, and mass spectrometry (MS) (46)(47)(48). These studies have suggested that the coordination of Cu(II) and Zn(II) in Ab species could occur via three histidine residues (H6, H13, and H14) and possibly another N-terminal residue or the peptide backbone.…”

Section: Aluminiummentioning

confidence: 99%

Metal ions, Alzheimer's disease and chelation therapy

Budimir¹

2011

Acta Pharmaceutica

176

113

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Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disease, clinically characterized by memory and cognitive dysfunctions. It is primarily a disease of old age (1) and is the most prevalent cause of dementia in elderly people (2). AD affects about 35 million people worldwide today (3) and it is estimated to nearly double every 20 years, to reach 66 million in 2030, and 115 million in 2050 (3). There is no known cause and no cure for AD and these numbers makes finding a cure or rational treatment for AD an urgent priority. Despite significant advances in understanding the neuropathological and neurochemical events taking place in AD, the etiopathogenesis of progressive and mental cognitive dysfunction associated with aging remains largely unclear.Pathologically, AD is characterized by neuronal degeneration. The brains of AD patients are mainly characterized by extracellular proteic (or neuritic) deposits (amyloid or senile plaques) surrounded by dystrophic neuritic and intracellular neurofibrillary tangles (NFT) (4). The plaques and tangles are present mainly in brain regions involved in learning and memory and emotional behavior such as the entorhinal cortex, hippocam- In the last few years, various studies have been providing evidence that metal ions are critically involved in the pathogenesis of major neurological diseases (Alzheimer, Parkinson). Metal ion chelators have been suggested as potential therapies for diseases involving metal ion imbalance. Neurodegeneration is an excellent target for exploiting the metal chelator approach to therapeutics. In contrast to the direct chelation approach in metal ion overload disorders, in neurodegeneration the goal seems to be a better and subtle modulation of metal ion homeostasis, aimed at restoring ionic balance. Thus, moderate chelators able to coordinate deleterious metals without disturbing metal homeostasis are needed. To date, several chelating agents have been investigated for their potential to treat neurodegeneration, and a series of 8-hydroxyquinoline analogues showed the greatest potential for the treatment of neurodegenerative diseases.

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“…In the case of neutrophils, Jansson et al [69] reported that exposure of these cells to low micromolar (≤5 µM) concentrations of HgCl 2 in vitro resulted in significant, albeit variable, increases in the production of superoxide activated by the chemoattractant, N-formyl-L-methionyl-L-leucyl-L-phenylalanine, but not with other activators such as PMA or opsonized zymosan. At approximately the same concentrations, HgCl 2 and MeHgCl were found to inhibit spontaneous apoptosis of human neutrophils in vitro [70], possibly by a mechanism related to induction of mild oxidative stress. At higher concentrations, however, the metal (in both studies) was found to become abruptly cytotoxic [69,70].…”

Section: Mercurymentioning

confidence: 85%

Harmful Interactions of Non-Essential Heavy Metals with Cells of the Innate Immune System

Theron¹,

Tintinger²,

Anderson³

2011

J Clin Toxicol

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Biological metals and Alzheimer's disease: Implications for therapeutics and diagnostics

Cited by 260 publications

References 319 publications

β-Amyloid Fibrils in Alzheimer Disease Are Not Inert When Bound to Copper Ions but Can Degrade Hydrogen Peroxide and Generate Reactive Oxygen Species

β-Amyloid Fibrils in Alzheimer Disease Are Not Inert When Bound to Copper Ions but Can Degrade Hydrogen Peroxide and Generate Reactive Oxygen Species

Metal ions, Alzheimer's disease and chelation therapy

Harmful Interactions of Non-Essential Heavy Metals with Cells of the Innate Immune System

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