title: Methylene blue protects against TDP-43 and FUS neuronal toxicity in C. elegans and D. rerio.
abstract: 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.
authors: Université de Montréal Hospital Research Centre, Montréal, Québec, Canada.
authors: Alexandra
authors: A
authors: Vaccaro
authors: Shunmoogum A
authors: SA
authors: Patten
authors: Sorana
authors: S
authors: Ciura
authors: Claudia
authors: C
authors: Maios
authors: Martine
authors: M
authors: Therrien
authors: Pierre
authors: P
authors: Drapeau
authors: Edor
authors: E
authors: Kabashi
authors: J Alex
authors: JA
authors: Parker
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008751:Methylene Blue / Q000008:administration & dosage / Q000494:pharmacology*; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D009154:Mutation; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010641:Phenotype; D034702:RNA-Binding Protein FUS / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D018696:Neuroprotective Agents; D034702:RNA-Binding Protein FUS; D008751:Methylene Blue