Endogenous Polyamines Reduce the Toxicity of Soluble A尾 Peptide Aggregates Associated with Alzheimer鈥檚 Disease

详细信息    查看全文

• 作者：Jinghui Luo ; Inayathulla Mohammed ; Sebastian K. T. S. W盲rml盲nder ; Yoshitaka Hiruma ; Astrid Gr盲slund ; Jan Pieter Abrahams
• 刊名：Biomacromolecules
• 出版年：2014
• 出版时间：June 9, 2014
• 年：2014
• 卷：15
• 期：6
• 页码：1985-1991
• 全文大小：467K
• 年卷期：v.15,no.6(June 9, 2014)
• ISSN：1526-4602

文摘

Polyamines promote the formation of the A尾 peptide amyloid fibers that are a hallmark of Alzheimer鈥檚 disease. Here we show that polyamines interact with nonaggregated A尾 peptides, thereby reducing the peptide鈥檚 hydrophobic surface. We characterized the associated conformational change through NMR titrations and molecular dynamics simulations. We found that even low concentrations of spermine, sperimidine, and putrescine fully protected SH-SY5Y (a neuronal cell model) against the most toxic conformational species of A尾, even at an A尾 oligomer concentration that would otherwise kill half of the cells or even more. These observations lead us to conclude that polyamines interfere with the more toxic prefibrillar conformations and might protect cells by promoting the structural transition of A尾 toward its less toxic fibrillar state that we reported previously. Since polyamines are present in brain fluid at the concentrations where we observed all these effects, their activity needs to be taken into account in understanding the molecular processes related to the development of Alzheimer鈥檚 disease.