Transthyretin Amyloidosis: Chaperone Concentration Changes and Increased Proteolysis in the Pathway to Disease.
Transthyretin amyloidosis is a conformational pathology characterized by the extracellular formation of amyloid deposits and the progressive impairment of the peripheral nervous system. Point mutations in this tetrameric plasma protein decrease its stability and are linked to disease onset and progr...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4492746?pdf=render |
| _version_ | 1818285739486478336 |
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| author | Gonçalo da Costa Cristina Ribeiro-Silva Raquel Ribeiro Samuel Gilberto Ricardo A Gomes António Ferreira Élia Mateus Eduardo Barroso Ana V Coelho Ana Ponces Freire Carlos Cordeiro |
| author_facet | Gonçalo da Costa Cristina Ribeiro-Silva Raquel Ribeiro Samuel Gilberto Ricardo A Gomes António Ferreira Élia Mateus Eduardo Barroso Ana V Coelho Ana Ponces Freire Carlos Cordeiro |
| author_sort | Gonçalo da Costa |
| collection | DOAJ |
| description | Transthyretin amyloidosis is a conformational pathology characterized by the extracellular formation of amyloid deposits and the progressive impairment of the peripheral nervous system. Point mutations in this tetrameric plasma protein decrease its stability and are linked to disease onset and progression. Since non-mutated transthyretin also forms amyloid in systemic senile amyloidosis and some mutation bearers are asymptomatic throughout their lives, non-genetic factors must also be involved in transthyretin amyloidosis. We discovered, using a differential proteomics approach, that extracellular chaperones such as fibrinogen, clusterin, haptoglobin, alpha-1-anti-trypsin and 2-macroglobulin are overrepresented in transthyretin amyloidosis. Our data shows that a complex network of extracellular chaperones are over represented in human plasma and we speculate that they act synergistically to cope with amyloid prone proteins. Proteostasis may thus be as important as point mutations in transthyretin amyloidosis. |
| first_indexed | 2024-12-13T01:13:29Z |
| format | Article |
| id | doaj.art-106c2bbc25cd438fb955ea5bf82f2744 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T01:13:29Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-106c2bbc25cd438fb955ea5bf82f27442022-12-22T00:04:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01107e012539210.1371/journal.pone.0125392Transthyretin Amyloidosis: Chaperone Concentration Changes and Increased Proteolysis in the Pathway to Disease.Gonçalo da CostaCristina Ribeiro-SilvaRaquel RibeiroSamuel GilbertoRicardo A GomesAntónio FerreiraÉlia MateusEduardo BarrosoAna V CoelhoAna Ponces FreireCarlos CordeiroTransthyretin amyloidosis is a conformational pathology characterized by the extracellular formation of amyloid deposits and the progressive impairment of the peripheral nervous system. Point mutations in this tetrameric plasma protein decrease its stability and are linked to disease onset and progression. Since non-mutated transthyretin also forms amyloid in systemic senile amyloidosis and some mutation bearers are asymptomatic throughout their lives, non-genetic factors must also be involved in transthyretin amyloidosis. We discovered, using a differential proteomics approach, that extracellular chaperones such as fibrinogen, clusterin, haptoglobin, alpha-1-anti-trypsin and 2-macroglobulin are overrepresented in transthyretin amyloidosis. Our data shows that a complex network of extracellular chaperones are over represented in human plasma and we speculate that they act synergistically to cope with amyloid prone proteins. Proteostasis may thus be as important as point mutations in transthyretin amyloidosis.http://europepmc.org/articles/PMC4492746?pdf=render |
| spellingShingle | Gonçalo da Costa Cristina Ribeiro-Silva Raquel Ribeiro Samuel Gilberto Ricardo A Gomes António Ferreira Élia Mateus Eduardo Barroso Ana V Coelho Ana Ponces Freire Carlos Cordeiro Transthyretin Amyloidosis: Chaperone Concentration Changes and Increased Proteolysis in the Pathway to Disease. PLoS ONE |
| title | Transthyretin Amyloidosis: Chaperone Concentration Changes and Increased Proteolysis in the Pathway to Disease. |
| title_full | Transthyretin Amyloidosis: Chaperone Concentration Changes and Increased Proteolysis in the Pathway to Disease. |
| title_fullStr | Transthyretin Amyloidosis: Chaperone Concentration Changes and Increased Proteolysis in the Pathway to Disease. |
| title_full_unstemmed | Transthyretin Amyloidosis: Chaperone Concentration Changes and Increased Proteolysis in the Pathway to Disease. |
| title_short | Transthyretin Amyloidosis: Chaperone Concentration Changes and Increased Proteolysis in the Pathway to Disease. |
| title_sort | transthyretin amyloidosis chaperone concentration changes and increased proteolysis in the pathway to disease |
| url | http://europepmc.org/articles/PMC4492746?pdf=render |
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