An Investigation of the Insulin Pathway and TDP-43 Based Amyotrophic Lateral Sclerosis

Persistent Link:
http://hdl.handle.net/10150/297742
Title:
An Investigation of the Insulin Pathway and TDP-43 Based Amyotrophic Lateral Sclerosis
Author:
Podolsky, Taylor Catherine
Issue Date:
2013
Publisher:
The University of Arizona.
Rights:
Copyright © 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.
Abstract:
The 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.
Type:
text; Electronic Thesis
Degree Name:
B.S.
Degree Level:
bachelors
Degree Program:
Honors College; Biology - Biomedical Studies
Degree Grantor:
University of Arizona
Advisor:
Zarnescu, Daniela C.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleAn Investigation of the Insulin Pathway and TDP-43 Based Amyotrophic Lateral Sclerosisen_US
dc.creatorPodolsky, Taylor Catherineen_US
dc.contributor.authorPodolsky, Taylor Catherineen_US
dc.date.issued2013-
dc.publisherThe University of Arizona.en_US
dc.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.en_US
dc.description.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.en_US
dc.typetexten_US
dc.typeElectronic Thesisen_US
thesis.degree.nameB.S.en_US
thesis.degree.levelbachelorsen_US
thesis.degree.disciplineHonors Collegeen_US
thesis.degree.disciplineBiology - Biomedical Studiesen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorZarnescu, Daniela C.-
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