scFv intrabody targeting wildtype TDP-43 presents protective effects in a cellular model of TDP-43 proteinopathy.
TDP-43 proteinopathies are neurological disorders marked by the abnormal accumulation of TDP-43 in the cytoplasm. This mislocalization disrupts the normal function of the protein. In most cases, it is the wildtype (wt) form of the protein that is involved. An untargeted high-throughput screen of a s...
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0322021 |
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| author | Yara Al Ojaimi Rudolf Hergesheimer Anna A Chami Hugo Alarcan Johanna Augros Audrey Dangoumau Shanez Haouari Jérôme Bourgeais Antoine Lefevre Samira Osman Patrick Emond Patrick Vourc'h Christian R Andres Philippe Corcia Olivier Herault Pierre Martineau Débora Lanznaster Hélène Blasco |
| author_facet | Yara Al Ojaimi Rudolf Hergesheimer Anna A Chami Hugo Alarcan Johanna Augros Audrey Dangoumau Shanez Haouari Jérôme Bourgeais Antoine Lefevre Samira Osman Patrick Emond Patrick Vourc'h Christian R Andres Philippe Corcia Olivier Herault Pierre Martineau Débora Lanznaster Hélène Blasco |
| author_sort | Yara Al Ojaimi |
| collection | DOAJ |
| description | TDP-43 proteinopathies are neurological disorders marked by the abnormal accumulation of TDP-43 in the cytoplasm. This mislocalization disrupts the normal function of the protein. In most cases, it is the wildtype (wt) form of the protein that is involved. An untargeted high-throughput screen of a single-chain variable fragment (scFv) library was performed using phage display against human full-length wt TDP-43. Two scFvs (B1 and D7) were retained following cellular expression (then termed intrabodies) and colocalization with cytoplasmic TDP-43 in vitro. We generated a 3D structure of full length wt TDP-43 in silico, and used it for epitope mapping. In a cellular model of TDP-43 proteinopathy, D7 enhanced the proteasomal degradation of the insoluble 35-kDa C-terminal fragment of TDP-43 and reversed some TDP-43-induced metabolomic alterations, particularly relating to the lipid metabolism. Our findings offer a new scFv intrabody that bind to human wtTDP-43 and modify cellular pathways associated with TDP-43 proteinopathies. |
| format | Article |
| id | doaj-art-6e25d50b876c48d8aa0de9dd77d3074b |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-6e25d50b876c48d8aa0de9dd77d3074b2025-08-20T03:37:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01208e032202110.1371/journal.pone.0322021scFv intrabody targeting wildtype TDP-43 presents protective effects in a cellular model of TDP-43 proteinopathy.Yara Al OjaimiRudolf HergesheimerAnna A ChamiHugo AlarcanJohanna AugrosAudrey DangoumauShanez HaouariJérôme BourgeaisAntoine LefevreSamira OsmanPatrick EmondPatrick Vourc'hChristian R AndresPhilippe CorciaOlivier HeraultPierre MartineauDébora LanznasterHélène BlascoTDP-43 proteinopathies are neurological disorders marked by the abnormal accumulation of TDP-43 in the cytoplasm. This mislocalization disrupts the normal function of the protein. In most cases, it is the wildtype (wt) form of the protein that is involved. An untargeted high-throughput screen of a single-chain variable fragment (scFv) library was performed using phage display against human full-length wt TDP-43. Two scFvs (B1 and D7) were retained following cellular expression (then termed intrabodies) and colocalization with cytoplasmic TDP-43 in vitro. We generated a 3D structure of full length wt TDP-43 in silico, and used it for epitope mapping. In a cellular model of TDP-43 proteinopathy, D7 enhanced the proteasomal degradation of the insoluble 35-kDa C-terminal fragment of TDP-43 and reversed some TDP-43-induced metabolomic alterations, particularly relating to the lipid metabolism. Our findings offer a new scFv intrabody that bind to human wtTDP-43 and modify cellular pathways associated with TDP-43 proteinopathies.https://doi.org/10.1371/journal.pone.0322021 |
| spellingShingle | Yara Al Ojaimi Rudolf Hergesheimer Anna A Chami Hugo Alarcan Johanna Augros Audrey Dangoumau Shanez Haouari Jérôme Bourgeais Antoine Lefevre Samira Osman Patrick Emond Patrick Vourc'h Christian R Andres Philippe Corcia Olivier Herault Pierre Martineau Débora Lanznaster Hélène Blasco scFv intrabody targeting wildtype TDP-43 presents protective effects in a cellular model of TDP-43 proteinopathy. PLoS ONE |
| title | scFv intrabody targeting wildtype TDP-43 presents protective effects in a cellular model of TDP-43 proteinopathy. |
| title_full | scFv intrabody targeting wildtype TDP-43 presents protective effects in a cellular model of TDP-43 proteinopathy. |
| title_fullStr | scFv intrabody targeting wildtype TDP-43 presents protective effects in a cellular model of TDP-43 proteinopathy. |
| title_full_unstemmed | scFv intrabody targeting wildtype TDP-43 presents protective effects in a cellular model of TDP-43 proteinopathy. |
| title_short | scFv intrabody targeting wildtype TDP-43 presents protective effects in a cellular model of TDP-43 proteinopathy. |
| title_sort | scfv intrabody targeting wildtype tdp 43 presents protective effects in a cellular model of tdp 43 proteinopathy |
| url | https://doi.org/10.1371/journal.pone.0322021 |
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