An evaluation of the self-assembly enhancing properties of cell-derived hexameric amyloid-β
Abstract A key hallmark of Alzheimer’s disease is the extracellular deposition of amyloid plaques composed primarily of the amyloidogenic amyloid-β (Aβ) peptide. The Aβ peptide is a product of sequential cleavage of the Amyloid Precursor Protein, the first step of which gives rise to a C-terminal Fr...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-90680-y |
| _version_ | 1818683321720242176 |
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| author | Devkee M. Vadukul Céline Vrancx Pierre Burguet Sabrina Contino Nuria Suelves Louise C. Serpell Loïc Quinton Pascal Kienlen-Campard |
| author_facet | Devkee M. Vadukul Céline Vrancx Pierre Burguet Sabrina Contino Nuria Suelves Louise C. Serpell Loïc Quinton Pascal Kienlen-Campard |
| author_sort | Devkee M. Vadukul |
| collection | DOAJ |
| description | Abstract A key hallmark of Alzheimer’s disease is the extracellular deposition of amyloid plaques composed primarily of the amyloidogenic amyloid-β (Aβ) peptide. The Aβ peptide is a product of sequential cleavage of the Amyloid Precursor Protein, the first step of which gives rise to a C-terminal Fragment (C99). Cleavage of C99 by γ-secretase activity releases Aβ of several lengths and the Aβ42 isoform in particular has been identified as being neurotoxic. The misfolding of Aβ leads to subsequent amyloid fibril formation by nucleated polymerisation. This requires an initial and critical nucleus for self-assembly. Here, we identify and characterise the composition and self-assembly properties of cell-derived hexameric Aβ42 and show its assembly enhancing properties which are dependent on the Aβ monomer availability. Identification of nucleating assemblies that contribute to self-assembly in this way may serve as therapeutic targets to prevent the formation of toxic oligomers. |
| first_indexed | 2024-12-17T10:32:53Z |
| format | Article |
| id | doaj.art-cffde72cfd7a458c9a29c038453f9d37 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-17T10:32:53Z |
| publishDate | 2021-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-cffde72cfd7a458c9a29c038453f9d372022-12-21T21:52:29ZengNature PortfolioScientific Reports2045-23222021-06-0111111710.1038/s41598-021-90680-yAn evaluation of the self-assembly enhancing properties of cell-derived hexameric amyloid-βDevkee M. Vadukul0Céline Vrancx1Pierre Burguet2Sabrina Contino3Nuria Suelves4Louise C. Serpell5Loïc Quinton6Pascal Kienlen-Campard7Alzheimer Research Group, Molecular and Cellular Division (CEMO), Institute of Neuroscience, Université Catholique de LouvainAlzheimer Research Group, Molecular and Cellular Division (CEMO), Institute of Neuroscience, Université Catholique de LouvainMass Spectrometry Laboratory, MolSys Research Unit, University of LiègeAlzheimer Research Group, Molecular and Cellular Division (CEMO), Institute of Neuroscience, Université Catholique de LouvainAlzheimer Research Group, Molecular and Cellular Division (CEMO), Institute of Neuroscience, Université Catholique de LouvainSussex Neuroscience, School of Life Sciences, University of SussexMass Spectrometry Laboratory, MolSys Research Unit, University of LiègeAlzheimer Research Group, Molecular and Cellular Division (CEMO), Institute of Neuroscience, Université Catholique de LouvainAbstract A key hallmark of Alzheimer’s disease is the extracellular deposition of amyloid plaques composed primarily of the amyloidogenic amyloid-β (Aβ) peptide. The Aβ peptide is a product of sequential cleavage of the Amyloid Precursor Protein, the first step of which gives rise to a C-terminal Fragment (C99). Cleavage of C99 by γ-secretase activity releases Aβ of several lengths and the Aβ42 isoform in particular has been identified as being neurotoxic. The misfolding of Aβ leads to subsequent amyloid fibril formation by nucleated polymerisation. This requires an initial and critical nucleus for self-assembly. Here, we identify and characterise the composition and self-assembly properties of cell-derived hexameric Aβ42 and show its assembly enhancing properties which are dependent on the Aβ monomer availability. Identification of nucleating assemblies that contribute to self-assembly in this way may serve as therapeutic targets to prevent the formation of toxic oligomers.https://doi.org/10.1038/s41598-021-90680-y |
| spellingShingle | Devkee M. Vadukul Céline Vrancx Pierre Burguet Sabrina Contino Nuria Suelves Louise C. Serpell Loïc Quinton Pascal Kienlen-Campard An evaluation of the self-assembly enhancing properties of cell-derived hexameric amyloid-β Scientific Reports |
| title | An evaluation of the self-assembly enhancing properties of cell-derived hexameric amyloid-β |
| title_full | An evaluation of the self-assembly enhancing properties of cell-derived hexameric amyloid-β |
| title_fullStr | An evaluation of the self-assembly enhancing properties of cell-derived hexameric amyloid-β |
| title_full_unstemmed | An evaluation of the self-assembly enhancing properties of cell-derived hexameric amyloid-β |
| title_short | An evaluation of the self-assembly enhancing properties of cell-derived hexameric amyloid-β |
| title_sort | evaluation of the self assembly enhancing properties of cell derived hexameric amyloid β |
| url | https://doi.org/10.1038/s41598-021-90680-y |
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