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Biogerontology

, Volume 7, Issue 5–6, pp 307–314 | Cite as

Oxidative stress and brain aging: is zinc the link?

  • V. Frazzini
  • E. Rockabrand
  • E. Mocchegiani
  • S. L. SensiEmail author
Research Article

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.

Keywords

Brain aging Zn2+ dysomeostasis Oxidative stress 

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

Notes

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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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • V. Frazzini
    • 1
  • E. Rockabrand
    • 4
  • E. Mocchegiani
    • 5
  • S. L. Sensi
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of Neurology, Molecular Neurology Unit, CeSI-Center for Excellence on AgingUniversity ‘G. d’Annunzio’ChietiItaly
  2. 2.Department of NeurologyUniversity of CaliforniaIrvineUSA
  3. 3.Department of NeurologyUniversity of Texas Medical BranchGalvestonUSA
  4. 4.Department of Psychiatry and Human BehaviorUniversity of CaliforniaIrvineUSA
  5. 5.Immunology Ctr. (Section: Nutrition, Immunity and Ageing) Res. Dept.INRCAAnconaItaly

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