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Monitoring Alzheimer Amyloid Peptide Aggregation by EPR

Plaques containing the aggregated β-Amyloid (Aβ) peptide in the brain are the main indicators of Alzheimer’s disease. Fibrils, the building blocks of plaques, can also be produced in vitro and consist of a regular arrangement of the peptide. The initial steps of fibril formation are not well underst...

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Autores principales: Sepkhanova, I., Drescher, M., Meeuwenoord, N. J., Limpens, R. W. A. L., Koning, R. I., Filippov, D. V., Huber, M.
Formato: Texto
Lenguaje:English
Publicado: Springer Vienna 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2779421/
https://www.ncbi.nlm.nih.gov/pubmed/19946595
http://dx.doi.org/10.1007/s00723-009-0019-1
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author Sepkhanova, I.
Drescher, M.
Meeuwenoord, N. J.
Limpens, R. W. A. L.
Koning, R. I.
Filippov, D. V.
Huber, M.
author_facet Sepkhanova, I.
Drescher, M.
Meeuwenoord, N. J.
Limpens, R. W. A. L.
Koning, R. I.
Filippov, D. V.
Huber, M.
author_sort Sepkhanova, I.
collection PubMed
description Plaques containing the aggregated β-Amyloid (Aβ) peptide in the brain are the main indicators of Alzheimer’s disease. Fibrils, the building blocks of plaques, can also be produced in vitro and consist of a regular arrangement of the peptide. The initial steps of fibril formation are not well understood and could involve smaller aggregates (oligomers) of Aβ. Such oligomers have even been implicated as the toxic agents. Here, a method to study oligomers on the time scale of aggregation is suggested. We have labeled the 40 residue Aβ peptide variant containing an N-terminal cysteine (cys-Aβ) with the MTSL [1-oxyl-2,2,5,5-tetramethyl-Δ-pyrroline-3-methyl] methanethiosulfonate spin label (SL-Aβ). Fibril formation in solutions of pure SL-Aβ and of SL-Aβ mixed with Aβ was shown by Congo-red binding and electron microscopy. Continuous-wave 9 GHz electron paramagnetic resonance reveals three fractions of different spin-label mobility: one attributed to monomeric Aβ, one to a multimer (8–15 monomers), and the last one to larger aggregates or fibrils. The approach, in principle, allows detection of oligomers on the time scale of aggregation.
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spelling pubmed-27794212009-11-23 Monitoring Alzheimer Amyloid Peptide Aggregation by EPR Sepkhanova, I. Drescher, M. Meeuwenoord, N. J. Limpens, R. W. A. L. Koning, R. I. Filippov, D. V. Huber, M. Appl Magn Reson Article Plaques containing the aggregated β-Amyloid (Aβ) peptide in the brain are the main indicators of Alzheimer’s disease. Fibrils, the building blocks of plaques, can also be produced in vitro and consist of a regular arrangement of the peptide. The initial steps of fibril formation are not well understood and could involve smaller aggregates (oligomers) of Aβ. Such oligomers have even been implicated as the toxic agents. Here, a method to study oligomers on the time scale of aggregation is suggested. We have labeled the 40 residue Aβ peptide variant containing an N-terminal cysteine (cys-Aβ) with the MTSL [1-oxyl-2,2,5,5-tetramethyl-Δ-pyrroline-3-methyl] methanethiosulfonate spin label (SL-Aβ). Fibril formation in solutions of pure SL-Aβ and of SL-Aβ mixed with Aβ was shown by Congo-red binding and electron microscopy. Continuous-wave 9 GHz electron paramagnetic resonance reveals three fractions of different spin-label mobility: one attributed to monomeric Aβ, one to a multimer (8–15 monomers), and the last one to larger aggregates or fibrils. The approach, in principle, allows detection of oligomers on the time scale of aggregation. Springer Vienna 2009-10-31 2009 /pmc/articles/PMC2779421/ /pubmed/19946595 http://dx.doi.org/10.1007/s00723-009-0019-1 Text en © The Author(s) 2009 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Article
Sepkhanova, I.
Drescher, M.
Meeuwenoord, N. J.
Limpens, R. W. A. L.
Koning, R. I.
Filippov, D. V.
Huber, M.
Monitoring Alzheimer Amyloid Peptide Aggregation by EPR
title Monitoring Alzheimer Amyloid Peptide Aggregation by EPR
title_full Monitoring Alzheimer Amyloid Peptide Aggregation by EPR
title_fullStr Monitoring Alzheimer Amyloid Peptide Aggregation by EPR
title_full_unstemmed Monitoring Alzheimer Amyloid Peptide Aggregation by EPR
title_short Monitoring Alzheimer Amyloid Peptide Aggregation by EPR
title_sort monitoring alzheimer amyloid peptide aggregation by epr
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2779421/
https://www.ncbi.nlm.nih.gov/pubmed/19946595
http://dx.doi.org/10.1007/s00723-009-0019-1
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