Potential pathogenic role of β-amyloid_1–42–aluminum complex in Alzheimer's disease

详细信息    查看全文

• 作者：Denise Drago ; Mikol Bettella ; Silvia Bolognin ; Laura Cendron ; Janez Scancar ; Radmila Milacic ; Fern ; a Ricchelli ; Angela Casini ; Luigi Messori ; Giuseppe Tognon ; Paolo Zatta
• 关键词：Alzheimer ; Aluminum ; Metal ions ; Membranes ; Neuroblastoma ; Fibrils
• 刊名：The International Journal of Biochemistry and Cell Biology
• 出版年：2008
• 出版时间：2008
• 年：2008
• 卷：40
• 期：4
• 页码：731-746
• 全文大小：1213 K

文摘

The etiopathogenesis of Alzheimer's disease is far from being clearly understood. However, the involvement of metal ions as a potential key factor towards conformational modifications and aggregation of amyloid is widely recognized. The aim of the present study is to shed some light on the relationship between metal ions, amyloid conformation/aggregation, and their potential relationship with the conformational aspects of AD. We compare the effects of β-amyloid_1–42 and its various metal complexes (β-amyloid–Al, β-amyloid–Zn, β-amyloid–Cu, β-amyloid–Fe) in human neuroblastoma cells in terms of cell viability, membrane structure properties, and cell morphology. No significant toxic effects were observed in neuroblastoma cells after 24 h treatment both with β-amyloid and β-amyloid–metals (β-amyloid–Zn, β-amyloid–Cu, β-amyloid–Fe); on the other hand, there was a marked reduction of cellular viability after treatment with β-amyloid–Al complex. In addition, treatment with β-amyloid–Al increased membrane fluidity much more than other β-amyloid–metal complexes, whose contribution was negligible. Furthermore, the cellular morphology, as observed by electron microscopy, was deeply altered by β-amyloid–Al. Importantly, β-amyloid–Al toxicity is closely and significantly associated with a great difference in the structure/aggregation of this complex with respect to that of β-amyloid alone and other β-amyloid–metal complexes. In addition, β-amyloid, as a consequence of Al binding, becomes strongly hydrophobic in character. These findings show a significant involvement of Al, compared to the other metal ions used in our experiments, in promoting a specific amyloid_1–42 aggregation, which is able to produce marked toxic effects on neuroblastoma cells, as clearly demonstrated for the first time in this study.