Oxidative stress and brain aging: is zinc the link?
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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.
KeywordsBrain aging Zn2+ dysomeostasis Oxidative stress
apoptosis inducing factor
mitochondrial membrane potential
mitochondrial permeability transition pore
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.
- Kujoth GC, Hiona A, Pugh TD, Someya S, Panzer K, Wohlgemuth SE, Hofer T, Seo AY, Sullivan R, Jobling WA, Morrow JD, Van Remmen H, Sedivy JM, Yamasoba T, Tanokura M, Weindruch R, Leeuwenburgh C, Prolla TA (2005) Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309:481–484PubMedCrossRefGoogle Scholar
- Mocchegiani E, Giacconi R, Fattoretti P, Casoli T, Cipriano C, Muti E, Malavolta M, DiStefano G, Bertoni-Freddari C (2004) Metallothionein isoforms (I+II and III) and interleukin-6 in the hippocampus of old rats: may their concomitant increments lead to neurodegeneration? Brain Res Bull 63:133–142PubMedCrossRefGoogle Scholar