Metals, oxidative stress and neurodegeneration: A focus on iron, manganese and mercury

► Oxidative stress (OS), particularly in mitochondria, is a common feature of iron (Fe), Mn and Hg toxicity. ► The primary molecular targets triggering of OS are distinct for each of the above metals. ► These metals are transported by distinct transporters. Essential metals are crucial for the maint...

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Bibliographic Details
Published in:Neurochemistry international 2013-04, Vol.62 (5), p.575-594
Main Authors: Farina, Marcelo, Avila, Daiana Silva, da Rocha, João Batista Teixeira, Aschner, Michael
Format: Article
Language:English
Subjects:
Glutathione
Humans
Iron
Iron - metabolism
Manganese
Manganese - metabolism
Mercury
Mercury - metabolism
Neurodegenerative Diseases - metabolism
Oxidative Stress
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Summary:► Oxidative stress (OS), particularly in mitochondria, is a common feature of iron (Fe), Mn and Hg toxicity. ► The primary molecular targets triggering of OS are distinct for each of the above metals. ► These metals are transported by distinct transporters. Essential metals are crucial for the maintenance of cell homeostasis. Among the 23 elements that have known physiological functions in humans, 12 are metals, including iron (Fe) and manganese (Mn). Nevertheless, excessive exposure to these metals may lead to pathological conditions, including neurodegeneration. Similarly, exposure to metals that do not have known biological functions, such as mercury (Hg), also present great health concerns. This review focuses on the neurodegenerative mechanisms and effects of Fe, Mn and Hg. Oxidative stress (OS), particularly in mitochondria, is a common feature of Fe, Mn and Hg toxicity. However, the primary molecular targets triggering OS are distinct. Free cationic iron is a potent pro-oxidant and can initiate a set of reactions that form extremely reactive products, such as OH. Mn can oxidize dopamine (DA), generating reactive species and also affect mitochondrial function, leading to accumulation of metabolites and culminating with OS. Cationic Hg forms have strong affinity for nucleophiles, such as –SH and –SeH. Therefore, they target critical thiol- and selenol-molecules with antioxidant properties. Finally, we address the main sources of exposure to these metals, their transport mechanisms into the brain, and therapeutic modalities to mitigate their neurotoxic effects.
ISSN:0197-0186
1872-9754
DOI:10.1016/j.neuint.2012.12.006