ZFIN ID: ZDB-PUB-120807-18
Methylene Blue Protects against TDP-43 and FUS Neuronal Toxicity in C. elegans and D. rerio
Vaccaro, A., Patten, S.A., Ciura, S., Maios, C., Therrien, M., Drapeau, P., Kabashi, E., and Parker, J.A.
Date: 2012
Source: PLoS One   7(7): e42117 (Journal)
Registered Authors: Drapeau, Pierre
Keywords: Methylene blue, Zebrafish, Caenorhabditis elegans, Motor neurons, Oxidative stress, Swimming, Phenotypes, Methylene Blue staining
MeSH Terms:
  • Animals
  • Behavior, Animal/drug effects
  • Caenorhabditis elegans/cytology*
  • Caenorhabditis elegans/drug effects
  • Caenorhabditis elegans/genetics
  • Caenorhabditis elegans/metabolism
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism*
  • Humans
  • Methylene Blue/administration & dosage
  • Methylene Blue/pharmacology*
  • Motor Neurons/drug effects
  • Motor Neurons/metabolism
  • Mutation
  • Neurons/drug effects*
  • Neurons/metabolism
  • Neuroprotective Agents/administration & dosage
  • Neuroprotective Agents/pharmacology*
  • Oxidative Stress/drug effects
  • Phenotype
  • RNA-Binding Protein FUS/genetics
  • RNA-Binding Protein FUS/metabolism*
  • Time Factors
  • Zebrafish/genetics
  • Zebrafish/metabolism*
PubMed: 22848727 Full text @ PLoS One

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 (S57”Δ 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.