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Amyloid Formation by Globular Proteins: The Need to Narrow the Gap Between in Vitro and in Vivo Mechanisms

The globular to fibrillar transition of proteins represents a key pathogenic event in the development of amyloid diseases. Although systemic amyloidoses share the common characteristic of amyloid deposition in the extracellular matrix, they are clinically heterogeneous as the affected organs may var...

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Autores principales: Faravelli, Giulia, Mondani, Valentina, Mangione, P. Patrizia, Raimondi, Sara, Marchese, Loredana, Lavatelli, Francesca, Stoppini, Monica, Corazza, Alessandra, Canetti, Diana, Verona, Guglielmo, Obici, Laura, Taylor, Graham W., Gillmore, Julian D., Giorgetti, Sofia, Bellotti, Vittorio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883118/
https://www.ncbi.nlm.nih.gov/pubmed/35237660
http://dx.doi.org/10.3389/fmolb.2022.830006
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author Faravelli, Giulia
Mondani, Valentina
Mangione, P. Patrizia
Raimondi, Sara
Marchese, Loredana
Lavatelli, Francesca
Stoppini, Monica
Corazza, Alessandra
Canetti, Diana
Verona, Guglielmo
Obici, Laura
Taylor, Graham W.
Gillmore, Julian D.
Giorgetti, Sofia
Bellotti, Vittorio
author_facet Faravelli, Giulia
Mondani, Valentina
Mangione, P. Patrizia
Raimondi, Sara
Marchese, Loredana
Lavatelli, Francesca
Stoppini, Monica
Corazza, Alessandra
Canetti, Diana
Verona, Guglielmo
Obici, Laura
Taylor, Graham W.
Gillmore, Julian D.
Giorgetti, Sofia
Bellotti, Vittorio
author_sort Faravelli, Giulia
collection PubMed
description The globular to fibrillar transition of proteins represents a key pathogenic event in the development of amyloid diseases. Although systemic amyloidoses share the common characteristic of amyloid deposition in the extracellular matrix, they are clinically heterogeneous as the affected organs may vary. The observation that precursors of amyloid fibrils derived from circulating globular plasma proteins led to huge efforts in trying to elucidate the structural events determining the protein metamorphosis from their globular to fibrillar state. Whereas the process of metamorphosis has inspired poets and writers from Ovid to Kafka, protein metamorphism is a more recent concept. It is an ideal metaphor in biochemistry for studying the protein folding paradigm and investigating determinants of folding dynamics. Although we have learned how to transform both normal and pathogenic globular proteins into fibrillar polymers in vitro, the events occurring in vivo, are far more complex and yet to be explained. A major gap still exists between in vivo and in vitro models of fibrillogenesis as the biological complexity of the disease in living organisms cannot be reproduced at the same extent in the test tube. Reviewing the major scientific attempts to monitor the amyloidogenic metamorphosis of globular proteins in systems of increasing complexity, from cell culture to human tissues, may help to bridge the gap between the experimental models and the actual pathological events in patients.
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spelling pubmed-88831182022-03-01 Amyloid Formation by Globular Proteins: The Need to Narrow the Gap Between in Vitro and in Vivo Mechanisms Faravelli, Giulia Mondani, Valentina Mangione, P. Patrizia Raimondi, Sara Marchese, Loredana Lavatelli, Francesca Stoppini, Monica Corazza, Alessandra Canetti, Diana Verona, Guglielmo Obici, Laura Taylor, Graham W. Gillmore, Julian D. Giorgetti, Sofia Bellotti, Vittorio Front Mol Biosci Molecular Biosciences The globular to fibrillar transition of proteins represents a key pathogenic event in the development of amyloid diseases. Although systemic amyloidoses share the common characteristic of amyloid deposition in the extracellular matrix, they are clinically heterogeneous as the affected organs may vary. The observation that precursors of amyloid fibrils derived from circulating globular plasma proteins led to huge efforts in trying to elucidate the structural events determining the protein metamorphosis from their globular to fibrillar state. Whereas the process of metamorphosis has inspired poets and writers from Ovid to Kafka, protein metamorphism is a more recent concept. It is an ideal metaphor in biochemistry for studying the protein folding paradigm and investigating determinants of folding dynamics. Although we have learned how to transform both normal and pathogenic globular proteins into fibrillar polymers in vitro, the events occurring in vivo, are far more complex and yet to be explained. A major gap still exists between in vivo and in vitro models of fibrillogenesis as the biological complexity of the disease in living organisms cannot be reproduced at the same extent in the test tube. Reviewing the major scientific attempts to monitor the amyloidogenic metamorphosis of globular proteins in systems of increasing complexity, from cell culture to human tissues, may help to bridge the gap between the experimental models and the actual pathological events in patients. Frontiers Media S.A. 2022-02-14 /pmc/articles/PMC8883118/ /pubmed/35237660 http://dx.doi.org/10.3389/fmolb.2022.830006 Text en Copyright © 2022 Faravelli, Mondani, Mangione, Raimondi, Marchese, Lavatelli, Stoppini, Corazza, Canetti, Verona, Obici, Taylor, Gillmore, Giorgetti and Bellotti. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Faravelli, Giulia
Mondani, Valentina
Mangione, P. Patrizia
Raimondi, Sara
Marchese, Loredana
Lavatelli, Francesca
Stoppini, Monica
Corazza, Alessandra
Canetti, Diana
Verona, Guglielmo
Obici, Laura
Taylor, Graham W.
Gillmore, Julian D.
Giorgetti, Sofia
Bellotti, Vittorio
Amyloid Formation by Globular Proteins: The Need to Narrow the Gap Between in Vitro and in Vivo Mechanisms
title Amyloid Formation by Globular Proteins: The Need to Narrow the Gap Between in Vitro and in Vivo Mechanisms
title_full Amyloid Formation by Globular Proteins: The Need to Narrow the Gap Between in Vitro and in Vivo Mechanisms
title_fullStr Amyloid Formation by Globular Proteins: The Need to Narrow the Gap Between in Vitro and in Vivo Mechanisms
title_full_unstemmed Amyloid Formation by Globular Proteins: The Need to Narrow the Gap Between in Vitro and in Vivo Mechanisms
title_short Amyloid Formation by Globular Proteins: The Need to Narrow the Gap Between in Vitro and in Vivo Mechanisms
title_sort amyloid formation by globular proteins: the need to narrow the gap between in vitro and in vivo mechanisms
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883118/
https://www.ncbi.nlm.nih.gov/pubmed/35237660
http://dx.doi.org/10.3389/fmolb.2022.830006
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