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https://hdl.handle.net/2440/66162
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Type: | Journal article |
Title: | Aβ40 and Aβ42 amyloid fibrils exhibit distinct molecular recycling |
Other Titles: | Abeta40 and Abeta42 amyloid fibrils exhibit distinct molecular recycling |
Author: | Sanchez, L. Madurga, S. Pukala, T. Vilaseca, M. Lopez-Iglesias, C. Robinson, C. Giralt, E. Carulla, N. |
Citation: | Journal of the American Chemical Society, 2011; 133(17):6505-6508 |
Publisher: | Amer Chemical Soc |
Issue Date: | 2011 |
ISSN: | 0002-7863 1520-5126 |
Statement of Responsibility: | Laia Sánchez, Sergio Madurga, Tara Pukala, Marta Vilaseca, Carmen López-Iglesias, Carol V. Robinson, Ernest Giralt, and Natàlia Carulla |
Abstract: | A critical aspect to understanding the molecular basis of Alzheimer's disease (AD) is the characterization of the kinetics of interconversion between the different species present during amyloid-β protein (Aβ) aggregation. By monitoring hydrogen/deuterium exchange in Aβ fibrils using electrospray ionization mass spectrometry, we demonstrate that the Aβ molecules comprising the fibril continuously dissociate and reassociate, resulting in molecular recycling within the fibril population. Investigations on Aβ40 and Aβ42 amyloid fibrils reveal that molecules making up Aβ40 fibrils recycle to a much greater extent than those of Aβ42. By examining factors that could influence molecular recycling and by running simulations, we show that the rate constant for dissociation of molecules from the fibril (k(off)) is much greater for Aβ40 than that for Aβ42. Importantly, the k(off) values obtained for Aβ40 and Aβ42 reveal that recycling occurs on biologically relevant time scales. These results have implications for understanding the role of Aβ fibrils in neurotoxicity and for designing therapeutic strategies against AD. |
Keywords: | Humans Alzheimer Disease Amyloid Peptide Fragments Spectrometry, Mass, Electrospray Ionization Amyloid beta-Peptides |
Rights: | © 2011 American Chemical Society |
DOI: | 10.1021/ja1117123 |
Published version: | http://dx.doi.org/10.1021/ja1117123 |
Appears in Collections: | Aurora harvest Chemistry publications |
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