Single Point Mutations Induce a Switch in the Molecular Mechanism of the Aggregation of the Alzheimer’s Disease Associated Aβ42 Peptide

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• 作者：Benedetta Bolognesi ; Samuel I. A. Cohen ; Pablo Aran Terol ; Elin K. Esbj?rner ; Sofia Giorgetti ; Maria F. Mossuto ; Antonino Natalello ; Ann-Christin Brorsson ; Tuomas P. J. Knowles ; Christopher M. Dobson ; Leila M. Luheshi
• 刊名：ACS Chemical Biology
• 出版年：2014
• 出版时间：February 21, 2014
• 年：2014
• 卷：9
• 期：2
• 页码：378-382
• 全文大小：289K
• ISSN：1554-8937

文摘

Single point mutations in the Alzheimer鈥檚 disease associated A尾₄₂ peptide are found to alter significantly its neurotoxic properties in vivo and have been associated with early onset forms of this devastating condition. We show that such mutations can induce structural changes in A尾₄₂ fibrils and are associated with a dramatic switch in the fibril-dependent mechanism by which A尾₄₂ aggregates. These observations reveal how subtle perturbations to the physicochemical properties of the A尾 peptide, and the structural properties of fibrils that it forms, can have profound effects on the mechanism of its aggregation and pathogenicity.