Elevated ferric, calcium and magnesium ions in the brain induce protein aggregation in brain mitochondria.

Alzheimer's disease and Parkinson's disease are two of several neurodegenerative disorders that affect the elderly. Although their aetiology remains uncertain, studies suggest that elevated aluminium or other metal ions in the brain directly influence the development of the histological abnormalities normally associated with these diseases; other investigations suggest that metal-ion-induced-dysfunction of mitochondria might be a critical factor. In this study, the impact of elevated aluminum (Al3+), ferric (Fe3+), calcium (Ca2+) and magnesium (Mg2+) ions on brain histology and on the protein composition of brain mitochondria were evaluated. Rabbits were injected intra-cerebrally with 1.4% solutions of either aluminium chloride (AlCl3), ferric chloride (FeCl3), calcium chloride (CaCl2) or magnesium chloride (MgCl2) and sacrificed 10 days later Histological analysis revealed that Al3+ but not the other ions induced neurofibrillary degeneration within the midbrain and medulla. Alternatively, SDS-PAGE revealed that Fe3+, Ca2+ and Mg2+ but not Al3+ induced alterations to the distribution of brain mitochondrial proteins. Both Fe3+ and Ca2+ triggered decreased concentration of three low molecular weight proteins (-7-14 kd) but Ca2+ precipitated their total absence. Both ions led to increased concentration of a high molecular weight protein (-110 kd). In contrast, Mg2 led to the total absence of the protein of lowest molecular weight (-7 kd) and increased concentration of a -36 kd protein. These results suggest that elevation of some metal ions in the brain induces protein aggregation with the nature of the aggregation being highly ion dependent. The results also point toward major differences between the histopathological effect of Al3+ and other ions.