title: Oxidative stress and brain aging: is zinc the link?
abstract: Zn(2+) dyshomeostasis has been strongly linked to neuronal injury in many neurological conditions. Toxic accumulation of intracellular free Zn(2+) ([Zn(2+)](i)) may result from either flux of the cation through glutamate receptor-associated channels, voltage-sensitive calcium channels, or Zn(2+)-sensitive membrane transporters. Injurious [Zn(2+)](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. Zn(2+) homeostasis is affected by oxidative stress, which is a potent trigger for detrimental Zn(2+) release from MTs. Interestingly, Zn(2+) 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 Zn(2+) dyshomeostasis and oxidative stress might act synergistically to promote aging-related neurodegeneration.
authors.affiliation: Department of Neurology, Molecular Neurology Unit, CeSI-Center for Excellence on Aging, University G. d'Annunzio, Chieti, 66013, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Frazzini
authors.forename: E
authors.initials: E
authors.lastname: Rockabrand
authors.forename: E
authors.initials: E
authors.lastname: Mocchegiani
authors.forename: S L
authors.initials: SL
authors.lastname: Sensi
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D027682:Cation Transport Proteins / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008668:Metallothionein / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009410:Nerve Degeneration; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; D017382:Reactive Oxygen Species; D008668:Metallothionein; D015032:Zinc