Biochemical view of aluminum-induced neurohazards.

The investigations summarized in this review demonstrate that at least in r at, ingestion of aluminum affects certain processes of central nervous syst em without causing generalized toxicity. The results of these investigation s indicate that short-term as well as long-term exposure to aluminum can ha ve deteriorating effects on the brain. The primary sites of action are stil l difficult to be identified from the variety of studies so far carried out using various in vivo and in vitro model systems. The effects of aluminum on central nervous system those have been recognised may be linked with the pathways leading to ultimate manifestation of neurotoxicity. The effects o f aluminum leading to manifestation of neurodisorders may arise form its in teraction with nervous system at various ways : (i) by interfering with the glucose metabolism leading to reduced formation of precursors of acetylcho line and binding with the catechol moiety of catecholamines, (ii) hy intera cting with Na+-K+ and Ca++ -Mg++ -ATPases resulting in alteration in the re lease and reuptake phenomena of excitatory amino acids and other neurotrasm itters by the pre-synaptic neuronal membrane, (iii) by acting as competitiv e inhibitor for calcium binding site on or within the channel causing modul ation in the intracellular calcium homeostasis, (iv) by increasing the cycl ic-AMP production as a result of inhibition of the ATPase activity of stimu latory of protein, As and thereby altering the functions of neuronal cells containing receptors coupled to cyclic-AMP, (v) by effecting changes in cyt osketetal proteins which might result from altered phosphorylations, proteo lysis, transport and synthesis, (vi) by interacting directly or indirectly with genomic structure and (vii) by inducing oxidative damage through lipid peroxidation of brain phospholipids. However, further studies are required to clarify whether neurotoxicity results from a series of directly connect ed events or represent the parallel processes following multiple effects of aluminum.