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Daf-2 Signaling Modifies Mutant SOD1 Toxicity in C. elegans

Authors
Journal
PLoS ONE
1932-6203
Publisher
Public Library of Science
Publication Date
Volume
7
Issue
3
Identifiers
DOI: 10.1371/journal.pone.0033494
Keywords
  • Research Article
  • Biology
  • Anatomy And Physiology
  • Physiological Processes
  • Model Organisms
  • Animal Models
  • Molecular Cell Biology
  • Signal Transduction
  • Signaling In Selected Disciplines
  • Medicine
  • Neurology
  • Motor Neuron Diseases
Disciplines
  • Biology
  • Medicine

Abstract

The DAF-2 Insulin/IGF-1 signaling (IIS) pathway is a strong modifier of Caenorhabditis elegans longevity and healthspan. As aging is the greatest risk factor for developing neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), we were interested in determining if DAF-2 signaling modifies disease pathology in mutant superoxide dismutase 1 (SOD1) expressing C. elegans. Worms with pan-neuronal G85R SOD1 expression demonstrate significantly impaired locomotion as compared to WT SOD1 expressing controls and they develop insoluble SOD1 aggregates. Reductions in DAF-2 signaling, either through a hypomorphic allele or neuronally targeted RNAi, decreases the abundance of aggregated SOD1 and results in improved locomotion in a DAF-16 dependant manner. These results suggest that manipulation of the DAF-2 Insulin/IGF-1 signaling pathway may have therapeutic potential for the treatment of ALS.

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