An Investigation of the Insulin Pathway and TDP-43 Based Amyotrophic Lateral Sclerosis
AuthorPodolsky, Taylor Catherine
AdvisorZarnescu, Daniela C.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractThe discovery of novel pathways and therapies in disease pathology is especially compelling in fatal neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s Disease. We have developed a Drosophila model for ALS based on the overexpression of five variants of humanTDP-43, an RNA-binding protein that has been linked to ALS and other neurodegenerative diseases. In our fly model we can reproduce many of the ALS human pathologies including diminished locomotor function, and shortened life span. A primary screen of 1200 FDA approved compounds was performed, which led to the identification of compounds which rescue lethality, including six different antidiabetic drugs. These drugs fell into three different categories, namely sulfonylureas, biguanides, and thiazolidinediones. Follow-up validations studies have shown locomotor function defects caused by TDP-43 toxicity. These findings suggest that antidiabetic drugs may have therapeutic potential for ALS.
Degree ProgramHonors College
Biology - Biomedical Studies