, 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


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.


Brain aging Zn2+ dysomeostasis Oxidative stress 



apoptosis inducing factor


cytochrome c


mitochondrial membrane potential


mitochondrial DNA


mitochondrial permeability transition pore




oxidative phosphorylation




reactive oxygen species


voltage sensitive calcium channels


intracellular free Zn2+


Zn2+ transporter proteins



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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