Iron inhibits neurotoxicity



Jesus consumed iron.

>J Biol Inorg Chem. 2004 Feb 3
>Iron inhibits neurotoxicity induced by trace copper and biological reductants.
>White AR, Barnham KJ, Huang X, Voltakis I, Beyreuther K, Masters CL, Cherny RA, Bush AI, Cappai R.
>Department of Pathology and Centre for Neuroscience, The University of Melbourne, 3010, Carlton
>South, Victoria, Australia.
>The extracellular microenvironment of the brain contains numerous biological redox agents,
>including ascorbate, glutathione, cysteine and homocysteine. During ischemia/reperfusion, aging or
>neurological disease, extracellular levels of reductants can increase dramatically owing to
>dysregulated homeostasis. The extracellular concentrations of transition metals such as copper and
>iron are also substantially elevated during aging and in some neurodegenerative disorders.
>Increases in the extracellular redox capacity can potentially generate neurotoxic free radicals
>from reduction of Cu(II) or Fe(III), resulting in neuronal cell death. To investigate this in
>vitro, the effects of extracellular reductants (ascorbate, glutathione, cysteine, homocysteine or
>methionine) on primary cortical neurons was examined. All redox agents except methionine induced
>widespread neuronal oxidative stress and subsequent cell death at concentrations occurring in
>normal conditions or during neurological insults. This neurotoxicity was totally dependent on trace
>Cu (>/=0.4 microM) already present in the culture medium and did not require addition of exogenous
>Cu. Toxicity involved generation of Cu(I) and H(2)O(2), while other trace metals did not induce
>toxicity. Surprisingly, administration of Fe(II) or Fe(III) (>/=2.5 microM) completely abrogated
>reductant-mediated neurotoxicity. The potent protective activity of Fe correlated with Fe
>inhibiting reductant-mediated Cu(I) and H(2)O(2) generation in cell-free assays and reduced
>cellular Cu uptake by neurons. This demonstrates a novel role for Fe in blocking Cu-mediated
>neurotoxicity in a high reducing environment. A possible pathogenic consequence for these phenomena
>was demonstrated by abrogation of Fe neuroprotection after pre-exposure of cultures to the
>Alzheimer's amyloid beta peptide (Abeta). The loss of Fe neuroprotection against reductant toxicity
>was greater after treatment with human Abeta1-42 than with human Abeta1-40 or rodent Abeta1-42,
>consistent with the central role of Abeta1-42 in Alzheimer's disease. These findings have important
>implications for trace biometal interactions and free radical-mediated damage during
>neurodegenerative illnesses such as Alzheimer's disease and old-age dementia.
>PMID: 14758525 [PubMed - as supplied by publisher]