Oteiza PI, Mackenzie GG, Verstraeten SV.
Metals in neurodegeneration: involvement of oxidants and oxidant-sensitive transcription factors.
Mol Aspects Med. 2004 Feb-Apr;25(1-2):103-15.
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When all that shines is not golden: Metals in Alzheimer disease
This review provides a good summary of the old and new mechanisms by which aluminium, zinc and lead might mediate neurotoxicity, and suggests that multiple downstream mechanism are involved. One additonal mechanism by which Pb might induce toxicity is via altered DNA methylation (e.g. Rossiello et al., 1991). Although it is suggested that Al based deodorants may add significantly to the neuronal pool of Al, this seems unlikely when compared to the daily intake of Al digested in foods (olfactory neurons rest safe!).
Upstream causes explaining the increase in the neuronal concentrations of these metal ions with aging remain to be determined, but might include changes in mitochondrial metabolism and/or changes in the expression/activity of metal ion transporters. Such changes might be mediated by reproductive hormones, as has been recently shown for the zinc transporter-ZnT3 (Lee et al., 2004).
Rossiello MR, Aresta AM, Prisco M, Kanduc D. (1991). DNA hypomethylation during liver cell proliferation induced by a single dose of lead nitrate. Boll Soc Ital Biol Sper. 67, 993-997. Abstract
Lee JY, Kim JH, Hong SH, Lee JY, Cherny RA, Bush AI, Palmiter RD, Koh JY. (2004). Estrogen decreases zinc transporter 3 expression and synaptic vesicle zinc levels in mouse brain.
J Biol Chem. 279, 8602-8607. Abstract