Trehalose Effect on The Aggregation of Model Proteins into Amyloid Fibrils
Protein aggregation into amyloid fibrils is a phenomenon that attracts attention from a wide and composite part of the scientific community. Indeed, the presence of mature fibrils is associated with several neurodegenerative diseases, and in addition these supramolecular aggregates are considered pr...
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MDPI AG
2020-05-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/10/5/60 |
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| author | Eleonora Mari Caterina Ricci Silvia Pieraccini Francesco Spinozzi Paolo Mariani Maria Grazia Ortore |
| author_facet | Eleonora Mari Caterina Ricci Silvia Pieraccini Francesco Spinozzi Paolo Mariani Maria Grazia Ortore |
| author_sort | Eleonora Mari |
| collection | DOAJ |
| description | Protein aggregation into amyloid fibrils is a phenomenon that attracts attention from a wide and composite part of the scientific community. Indeed, the presence of mature fibrils is associated with several neurodegenerative diseases, and in addition these supramolecular aggregates are considered promising self-assembling nanomaterials. In this framework, investigation on the effect of cosolutes on protein propensity to aggregate into fibrils is receiving growing interest, and new insights on this aspect might represent valuable steps towards comprehension of highly complex biological processes. In this work we studied the influence exerted by the osmolyte trehalose on fibrillation of two model proteins, that is, lysozyme and insulin, investigated during concomitant variation of the solution ionic strength due to NaCl. In order to monitor both secondary structures and the overall tridimensional conformations, we have performed UV spectroscopy measurements with Congo Red, Circular Dichroism, and synchrotron Small Angle X-ray Scattering. For both proteins we describe the effect of trehalose in changing the fibrillation pattern and, as main result, we observe that ionic strength in solution is a key factor in determining trehalose efficiency in slowing down or blocking protein fibrillation. Ionic strength reveals to be a competitive element with respect to trehalose, being able to counteract its inhibiting effects toward amyloidogenesis. Reported data highlight the importance of combining studies carried out on cosolutes with valuation of other physiological parameters that may affect the aggregation process. Also, the obtained experimental results allow to hypothesize a plausible mechanism adopted by the osmolyte to preserve protein surface and prevent protein fibrillation. |
| first_indexed | 2024-03-10T19:52:01Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-10T19:52:01Z |
| publishDate | 2020-05-01 |
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| record_format | Article |
| series | Life |
| spelling | doaj.art-ea337b9363fa4f8ab3c37bdf86d189bc2023-11-20T00:19:27ZengMDPI AGLife2075-17292020-05-011056010.3390/life10050060Trehalose Effect on The Aggregation of Model Proteins into Amyloid FibrilsEleonora Mari0Caterina Ricci1Silvia Pieraccini2Francesco Spinozzi3Paolo Mariani4Maria Grazia Ortore5Department of Life and Environmental Sciences, Polytechnic University of Marche, I-60121 Ancona, ItalyDepartment of Life and Environmental Sciences, Polytechnic University of Marche, I-60121 Ancona, ItalyDepartment of Chemistry “Giacomo Ciamician”, University of Bologna, I-40126 Bologna, ItalyDepartment of Life and Environmental Sciences, Polytechnic University of Marche, I-60121 Ancona, ItalyDepartment of Life and Environmental Sciences, Polytechnic University of Marche, I-60121 Ancona, ItalyDepartment of Life and Environmental Sciences, Polytechnic University of Marche, I-60121 Ancona, ItalyProtein aggregation into amyloid fibrils is a phenomenon that attracts attention from a wide and composite part of the scientific community. Indeed, the presence of mature fibrils is associated with several neurodegenerative diseases, and in addition these supramolecular aggregates are considered promising self-assembling nanomaterials. In this framework, investigation on the effect of cosolutes on protein propensity to aggregate into fibrils is receiving growing interest, and new insights on this aspect might represent valuable steps towards comprehension of highly complex biological processes. In this work we studied the influence exerted by the osmolyte trehalose on fibrillation of two model proteins, that is, lysozyme and insulin, investigated during concomitant variation of the solution ionic strength due to NaCl. In order to monitor both secondary structures and the overall tridimensional conformations, we have performed UV spectroscopy measurements with Congo Red, Circular Dichroism, and synchrotron Small Angle X-ray Scattering. For both proteins we describe the effect of trehalose in changing the fibrillation pattern and, as main result, we observe that ionic strength in solution is a key factor in determining trehalose efficiency in slowing down or blocking protein fibrillation. Ionic strength reveals to be a competitive element with respect to trehalose, being able to counteract its inhibiting effects toward amyloidogenesis. Reported data highlight the importance of combining studies carried out on cosolutes with valuation of other physiological parameters that may affect the aggregation process. Also, the obtained experimental results allow to hypothesize a plausible mechanism adopted by the osmolyte to preserve protein surface and prevent protein fibrillation.https://www.mdpi.com/2075-1729/10/5/60small angle X-ray scatteringcircular dichroismspectroscopyamyloidtrehaloseprotein solvation |
| spellingShingle | Eleonora Mari Caterina Ricci Silvia Pieraccini Francesco Spinozzi Paolo Mariani Maria Grazia Ortore Trehalose Effect on The Aggregation of Model Proteins into Amyloid Fibrils Life small angle X-ray scattering circular dichroism spectroscopy amyloid trehalose protein solvation |
| title | Trehalose Effect on The Aggregation of Model Proteins into Amyloid Fibrils |
| title_full | Trehalose Effect on The Aggregation of Model Proteins into Amyloid Fibrils |
| title_fullStr | Trehalose Effect on The Aggregation of Model Proteins into Amyloid Fibrils |
| title_full_unstemmed | Trehalose Effect on The Aggregation of Model Proteins into Amyloid Fibrils |
| title_short | Trehalose Effect on The Aggregation of Model Proteins into Amyloid Fibrils |
| title_sort | trehalose effect on the aggregation of model proteins into amyloid fibrils |
| topic | small angle X-ray scattering circular dichroism spectroscopy amyloid trehalose protein solvation |
| url | https://www.mdpi.com/2075-1729/10/5/60 |
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