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Different Chronic Stress Paradigms Converge on Endogenous TDP43 Cleavage and Aggregation
The TAR-DNA binding protein (TDP43) is a nuclear protein whose cytoplasmic inclusions are hallmarks of Amyotrophic Lateral Sclerosis (ALS). Acute stress in cells causes TDP43 mobilization to the cytoplasm and its aggregation through different routes. Although acute stress elicits a strong phenotype,...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10533643/ https://www.ncbi.nlm.nih.gov/pubmed/37450246 http://dx.doi.org/10.1007/s12035-023-03455-z |
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author | Candelise, Niccolò Caissutti, Daniela Zenuni, Henri Nesci, Valentina Scaricamazza, Silvia Salvatori, Illari Spinello, Zaira Mattei, Vincenzo Garofalo, Tina Ferri, Alberto Valle, Cristiana Misasi, Roberta |
author_facet | Candelise, Niccolò Caissutti, Daniela Zenuni, Henri Nesci, Valentina Scaricamazza, Silvia Salvatori, Illari Spinello, Zaira Mattei, Vincenzo Garofalo, Tina Ferri, Alberto Valle, Cristiana Misasi, Roberta |
author_sort | Candelise, Niccolò |
collection | PubMed |
description | The TAR-DNA binding protein (TDP43) is a nuclear protein whose cytoplasmic inclusions are hallmarks of Amyotrophic Lateral Sclerosis (ALS). Acute stress in cells causes TDP43 mobilization to the cytoplasm and its aggregation through different routes. Although acute stress elicits a strong phenotype, is far from recapitulating the years-long aggregation process. We applied different chronic stress protocols and described TDP43 aggregation in a human neuroblastoma cell line by combining solubility assays, thioflavin-based microscopy and flow cytometry. This approach allowed us to detect, for the first time to our knowledge in vitro, the formation of 25 kDa C-terminal fragment of TDP43, a pathogenic hallmark of ALS. Our results indicate that chronic stress, compared to the more common acute stress paradigm, better recapitulates the cell biology of TDP43 proteinopathies. Moreover, we optimized a protocol for the detection of bona fide prions in living cells, suggesting that TDP43 may form amyloids as a stress response. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12035-023-03455-z. |
format | Online Article Text |
id | pubmed-10533643 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-105336432023-09-29 Different Chronic Stress Paradigms Converge on Endogenous TDP43 Cleavage and Aggregation Candelise, Niccolò Caissutti, Daniela Zenuni, Henri Nesci, Valentina Scaricamazza, Silvia Salvatori, Illari Spinello, Zaira Mattei, Vincenzo Garofalo, Tina Ferri, Alberto Valle, Cristiana Misasi, Roberta Mol Neurobiol Original Article The TAR-DNA binding protein (TDP43) is a nuclear protein whose cytoplasmic inclusions are hallmarks of Amyotrophic Lateral Sclerosis (ALS). Acute stress in cells causes TDP43 mobilization to the cytoplasm and its aggregation through different routes. Although acute stress elicits a strong phenotype, is far from recapitulating the years-long aggregation process. We applied different chronic stress protocols and described TDP43 aggregation in a human neuroblastoma cell line by combining solubility assays, thioflavin-based microscopy and flow cytometry. This approach allowed us to detect, for the first time to our knowledge in vitro, the formation of 25 kDa C-terminal fragment of TDP43, a pathogenic hallmark of ALS. Our results indicate that chronic stress, compared to the more common acute stress paradigm, better recapitulates the cell biology of TDP43 proteinopathies. Moreover, we optimized a protocol for the detection of bona fide prions in living cells, suggesting that TDP43 may form amyloids as a stress response. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12035-023-03455-z. Springer US 2023-07-14 2023 /pmc/articles/PMC10533643/ /pubmed/37450246 http://dx.doi.org/10.1007/s12035-023-03455-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Candelise, Niccolò Caissutti, Daniela Zenuni, Henri Nesci, Valentina Scaricamazza, Silvia Salvatori, Illari Spinello, Zaira Mattei, Vincenzo Garofalo, Tina Ferri, Alberto Valle, Cristiana Misasi, Roberta Different Chronic Stress Paradigms Converge on Endogenous TDP43 Cleavage and Aggregation |
title | Different Chronic Stress Paradigms Converge on Endogenous TDP43 Cleavage and Aggregation |
title_full | Different Chronic Stress Paradigms Converge on Endogenous TDP43 Cleavage and Aggregation |
title_fullStr | Different Chronic Stress Paradigms Converge on Endogenous TDP43 Cleavage and Aggregation |
title_full_unstemmed | Different Chronic Stress Paradigms Converge on Endogenous TDP43 Cleavage and Aggregation |
title_short | Different Chronic Stress Paradigms Converge on Endogenous TDP43 Cleavage and Aggregation |
title_sort | different chronic stress paradigms converge on endogenous tdp43 cleavage and aggregation |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10533643/ https://www.ncbi.nlm.nih.gov/pubmed/37450246 http://dx.doi.org/10.1007/s12035-023-03455-z |
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