Artikel
High dietary intake of iron and aluminum promotes disease progression in a transgenic mousemodel of Parkinson’s disease
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Veröffentlicht: | 11. September 2012 |
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Introduction: Parkinson's Disease (PD) is characterized by pathological protein aggregates in neuronal cells that are mainly composed of alpha-synuclein (a-syn). Small oligomeric precursors of fibrillar a-syn aggregates are presumed to be the main toxic particle species in the pathogenesis of PD by forming pores in lipid bilayers. Many studies suggest a metal ion dependent aggregation of a-syn. Furthermore, it was shown that the formation of pore-forming a-syn oligomers in vitro can be induced by trivalent metal ions such as iron (Fe) and aluminum (Al).
Aim: To investigate the impact of dietary intake of Fe and Al on disease progression in an a-syn transgenic mouse model of PD.
Methods:Transgenic (tg) mice expressing human A30P-a-syn were exposed to either high concentrations of Fe (600 mg/kg food pellets) or Al (600 mg/kg food pellets) using metal ion enriched food pellets. Tg control mice received a diet containing concentrations of 60 mg/kg (Fe) and
Results: In this tg a-syn overexpressing mouse model an elevated dietary uptake of Fe or Al, respectively, resulted in faster disease progression with an earlier decline of motor performance and a shorter lifespan. A significant increase in the amount of cellular a-syn aggregates was found in tg mice treated with diets containing a high concentration of either Fe or Al when compared to mice fed with the control diet. Wt mice neither displayed any signs of toxicity, nor a decrease in motor performance nor any histopathological changes in neuronal cells.
Conclusion: These date corroborate the important influence of trivalent metal ions on disease progression in synucleinopathies such as PD in vivo by enhancing a-syn aggregation. This highlights the interplay of a-syn and metal ions in neurodegeneration and confirms data from previous in vitro and epidemiological studies which also suggest an important role of trivalent metal ions in the pathogenesis of PD.