Oxidative stress and brain aging: is zinc the link?
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.
Frazzini
V
V
Department of Neurology, Molecular Neurology Unit, CeSI-Center for Excellence on Aging, University G. d'Annunzio, Chieti, 66013, Italy.
Rockabrand
E
E
Mocchegiani
E
E
Sensi
S L
SL
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*
D027682:Cation Transport Proteins; D017382:Reactive Oxygen Species; D008668:Metallothionein; D015032:Zinc