The Effects of the Insulin Signaling Pathway on TDP-43 Toxicity in Amyotrophic Lateral Sclerosis

Abstract

The causes of Amyotrophic Lateral Sclerosis, a fatal neurodegenerative disease that results in skeletal muscle paralysis, are not clear; however, the nuclear RNA-binding protein TDP-43 has been suggested to play a critical role in ALS pathology. A previous drug screen that demonstrated lethality rescue in flies administered anti-diabetic drugs hinted that perhaps the Insulin signaling pathway in motor neurons might be mediating TDP-43 toxicity. Therefore, our original hypothesis was simple in that we reasoned that the insulin pathway was interacting with TDP-43. Eventually, our larval turning, lethality and eye phenotype assays have allowed us to further hypothesize that insulin resistance in motor neurons is contributing to TDP-43 neurotoxicity.