TY - JOUR
T1 - Metals, oxidative stress and neurodegeneration
T2 - A focus on iron, manganese and mercury
AU - Farina, Marcelo
AU - Avila, Daiana Silva
AU - Da Rocha, João Batista Teixeira
AU - Aschner, Michael
N1 - Funding Information:
The authors would like to thank their colleagues/co-authors who have contributed to several studies referenced in this review. These studies were funded in part by grants from (in alphabetical order): Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq, INCT for Excitotoxicity and Neuroprotection-MCT/CNPq and IBNnet/CNPq, Brazil (Daiana S. Ávila, João B.T. Rocha and M. Farina); Fundação de Amparo à Pesquisa do Estado de Santa Catarina, Brazil (M. Farina); Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil (Daiana S. Ávila and João B.T. Rocha); US Public Health Service grants from the National Institute of Environmental Health Sciences (NIEHS) R01 ES10563 and R01 ES07331 (M. Aschner).
PY - 2013/4
Y1 - 2013/4
N2 - 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.
AB - 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.
KW - Glutathione
KW - Iron
KW - Manganese
KW - Mercury
KW - Oxidative stress
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U2 - 10.1016/j.neuint.2012.12.006
DO - 10.1016/j.neuint.2012.12.006
M3 - Review article
C2 - 23266600
AN - SCOPUS:84875691670
SN - 0197-0186
VL - 62
SP - 575
EP - 594
JO - Neurochemistry International
JF - Neurochemistry International
IS - 5
ER -