Beta-amyloid toxicity increases with hydrophobicity in the presence of metal ions
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Alzheimer’s disease is a multifactorial neurodegenerative disorder characterized by the pathological brain deposition of neurofibrillary tangles and senile plaques. The latter consist mainly of insoluble β-amyloid (Aβ) fibril deposition. Aβ aggregation and deposition can be increased by several factors, including metal ions. In this study we investigated the role played by metal ions in affecting Aβ oligomerization in the presence and in the absence of its hydrophobic fragment Aβ17–28. This was done not as a physiological investigation, but as a paradigmatic study to confirm the key role of Aβ superficial hydrophobicity as a relevant aggravating factor that contributes to the toxicity of Aβ and Aβ–metal complexes. The structural conformations of Aβ–metal complexes were monitored through fluorescence and turbidity measurements as well as transmission electron microscopy. Results reported herein indicate that various metals differentially influence Aβ conformation, with aluminum being the only metal ion for which we are able to determine a dramatic enhancement of peptide oligomer formation with a consequent toxic effect. This scenario was further enhanced by the presence of Aβ17–28, which resulted in a marked toxicity in a neuroblastoma cell culture as a consequence of the enhancement of the hydrophobicity of the amyloid and amyloid–metal complexes.
KeywordsAmyloid-beta Aluminum Alzheimer’s disease Metal ions Hydrophobicity
This work was supported by PRIN 2007.
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