Metals in neurodegeneration: involvement of oxidants and oxidant-sensitive transcription factors.

Oxidant-mediated damage and the triggering of oxidant-sensitive transcription factors could be associated with the neurotoxic actions of aluminum, zinc and lead. Aluminum and lead could induce oxidative stress through their capacity to interact with active oxygen species, increasing their oxidant activity, or by affecting membrane rheology. Aluminum-membrane interactions can also affect signaling cascades. Zinc, at high and low concentrations, increases cell oxidant concentrations, affects AP-1 and NF-kappaB transcription factors and induces neuronal cell death. The capacity of lead to promote oxidative stress, affect cell signals and to induce cell death by apoptosis has been mostly attributed to its effect on different calcium-mediated cellular events. The mentioned mechanisms as well as the contribution of these metals to different neurodegenerative disorders are discussed.