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Oxidative stress and brain aging: is zinc the link?

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Abstract

Zn2+ dyshomeostasis has been strongly linked to neuronal injury in many neurological conditions. Toxic accumulation of intracellular free Zn2+ ([Zn2+]i) may result from either flux of the cation through glutamate receptor-associated channels, voltage-sensitive calcium channels, or Zn2+-sensitive membrane transporters. Injurious [Zn2+]i rises can also result from release of the cation from intracellular sites such as metallothioneins (MTs) and mitochondria. Chronic inflammation and oxidative stress are hallmarks of aging. Zn2+ homeostasis is affected by oxidative stress, which is a potent trigger for detrimental Zn2+ release from MTs. Interestingly, Zn2+ itself is a strong inducer of oxidative stress by promoting mitochondrial and extra-mitochondrial production of reactive oxygen species. In this review, we examine how Zn2+ dyshomeostasis and oxidative stress might act synergistically to promote aging-related neurodegeneration.

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Abbreviations

AIF:

apoptosis inducing factor

Cyt-c:

cytochrome c

ΔΨm :

mitochondrial membrane potential

mtDNA:

mitochondrial DNA

mPTP:

mitochondrial permeability transition pore

MTs:

metallothioneins

OXPHOS:

oxidative phosphorylation

ONOO- :

peroxynitrite

ROS:

reactive oxygen species

VSCCs:

voltage sensitive calcium channels

[Zn2+]I :

intracellular free Zn2+

ZnTs:

Zn2+ transporter proteins

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Acknowledgments

This work was supported by PRIN 2004, FIRB 2003 (SLS); INRCA, Italian Health Ministry (RF. 206-2002 to EM), and European Commission (Zincage project n. FOOD-CT-506850; EM) grants.

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Authors and Affiliations

  1. Department of Neurology, Molecular Neurology Unit, CeSI-Center for Excellence on Aging, University ‘G. d’Annunzio’, Chieti, 66013, Italy

    V. Frazzini & S. L. Sensi

  2. Department of Neurology, University of California, Irvine, CA, 92697-4292, USA

    S. L. Sensi

  3. Department of Neurology, University of Texas Medical Branch, Galveston, TX, 77555-0539, USA

    S. L. Sensi

  4. Department of Psychiatry and Human Behavior, University of California, Irvine, CA, 92697, USA

    E. Rockabrand

  5. Immunology Ctr. (Section: Nutrition, Immunity and Ageing) Res. Dept., INRCA, via Birarelli 8, 60121, Ancona, Italy

    E. Mocchegiani

Authors
  1. V. Frazzini
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  2. E. Rockabrand
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  3. E. Mocchegiani
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  4. S. L. Sensi
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Corresponding author

Correspondence to S. L. Sensi.

Additional information

Presented at the ZincAge Conference, Madrid, February 10–13, 2006

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Frazzini, V., Rockabrand, E., Mocchegiani, E. et al. Oxidative stress and brain aging: is zinc the link?. Biogerontology 7, 307–314 (2006). https://doi.org/10.1007/s10522-006-9045-7

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  • DOI: https://doi.org/10.1007/s10522-006-9045-7

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