Methylene blue protects against TDP-43 and FUS neuronal toxicity in C. elegans and D. rerio.
The DNA/RNA-binding proteins TDP-43 and FUS are found in protein aggregates in a growing number of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and related dementia, but little is known about the neurotoxic mechanisms. We have generated Caenorhabditis elegans and zebrafi...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0042117&type=printable |
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| author | Alexandra Vaccaro Shunmoogum A Patten Sorana Ciura Claudia Maios Martine Therrien Pierre Drapeau Edor Kabashi J Alex Parker |
| author_facet | Alexandra Vaccaro Shunmoogum A Patten Sorana Ciura Claudia Maios Martine Therrien Pierre Drapeau Edor Kabashi J Alex Parker |
| author_sort | Alexandra Vaccaro |
| collection | DOAJ |
| description | The DNA/RNA-binding proteins TDP-43 and FUS are found in protein aggregates in a growing number of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and related dementia, but little is known about the neurotoxic mechanisms. We have generated Caenorhabditis elegans and zebrafish animal models expressing mutant human TDP-43 (A315T or G348C) or FUS (S57Δ or R521H) that reflect certain aspects of ALS including motor neuron degeneration, axonal deficits, and progressive paralysis. To explore the potential of our humanized transgenic C. elegans and zebrafish in identifying chemical suppressors of mutant TDP-43 and FUS neuronal toxicity, we tested three compounds with potential neuroprotective properties: lithium chloride, methylene blue and riluzole. We identified methylene blue as a potent suppressor of TDP-43 and FUS toxicity in both our models. Our results indicate that methylene blue can rescue toxic phenotypes associated with mutant TDP-43 and FUS including neuronal dysfunction and oxidative stress. |
| format | Article |
| id | doaj-art-e4b8648f7d3a4e61846ae8092628a8bc |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-e4b8648f7d3a4e61846ae8092628a8bc2025-08-20T02:43:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0177e4211710.1371/journal.pone.0042117Methylene blue protects against TDP-43 and FUS neuronal toxicity in C. elegans and D. rerio.Alexandra VaccaroShunmoogum A PattenSorana CiuraClaudia MaiosMartine TherrienPierre DrapeauEdor KabashiJ Alex ParkerThe DNA/RNA-binding proteins TDP-43 and FUS are found in protein aggregates in a growing number of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and related dementia, but little is known about the neurotoxic mechanisms. We have generated Caenorhabditis elegans and zebrafish animal models expressing mutant human TDP-43 (A315T or G348C) or FUS (S57Δ or R521H) that reflect certain aspects of ALS including motor neuron degeneration, axonal deficits, and progressive paralysis. To explore the potential of our humanized transgenic C. elegans and zebrafish in identifying chemical suppressors of mutant TDP-43 and FUS neuronal toxicity, we tested three compounds with potential neuroprotective properties: lithium chloride, methylene blue and riluzole. We identified methylene blue as a potent suppressor of TDP-43 and FUS toxicity in both our models. Our results indicate that methylene blue can rescue toxic phenotypes associated with mutant TDP-43 and FUS including neuronal dysfunction and oxidative stress.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0042117&type=printable |
| spellingShingle | Alexandra Vaccaro Shunmoogum A Patten Sorana Ciura Claudia Maios Martine Therrien Pierre Drapeau Edor Kabashi J Alex Parker Methylene blue protects against TDP-43 and FUS neuronal toxicity in C. elegans and D. rerio. PLoS ONE |
| title | Methylene blue protects against TDP-43 and FUS neuronal toxicity in C. elegans and D. rerio. |
| title_full | Methylene blue protects against TDP-43 and FUS neuronal toxicity in C. elegans and D. rerio. |
| title_fullStr | Methylene blue protects against TDP-43 and FUS neuronal toxicity in C. elegans and D. rerio. |
| title_full_unstemmed | Methylene blue protects against TDP-43 and FUS neuronal toxicity in C. elegans and D. rerio. |
| title_short | Methylene blue protects against TDP-43 and FUS neuronal toxicity in C. elegans and D. rerio. |
| title_sort | methylene blue protects against tdp 43 and fus neuronal toxicity in c elegans and d rerio |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0042117&type=printable |
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