Characterization of insulin signaling in a Caenorhabditis elegans Alzheimer’s disease model
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Authors
Chiu, Hilton
Date
Type
thesis
Language
eng
Keyword
Alzheimer's , insulin , genetics , molecular biology , neurobiology
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Abstract
Insulin is a key hormone in the regulation of blood glucose levels in many animals. Dysfunctional insulin signaling is one of the leading mechanisms of interest for the pathogenesis of diabetes and Alzheimer’s disease (AD). Despite the claim of a link between diabetes and AD, the results in the literature have been incongruent. Some studies have claimed that insulin resistance is a major implication of AD, while others have reported that the risk is increased by excess insulin in the blood. Using the microscopic worm, Caenorhabditis elegans, we have developed a model to study the link between insulin signaling and AD pathologies, including changes in neuronal morphology and abnormal behaviour. Furthermore, we have examined the effects of hyperactive insulin signaling on the expression of the two characteristic proteins of AD, amyloid-beta and tau. By genetically modifying the key players of the insulin-signaling pathway and the 40 insulin-like peptides in C. elegans, we may be able to identify novel targets for the prevention or treatment of AD. In this research, we tested whether the 40 insulin-like peptides are inhibitors or activators of the insulin-signaling pathway, based on the aforementioned phenotypes associated with AD. Alternatively, some of these 40 insulin-like peptides may work through the non-canonical insulin-signaling pathway, with the potential of pointing us to novel genetic interactors. Our work has shown that of the 40 insulin-like peptides, some exacerbated AD-related pathologies, while others reduced them. Understanding the function of the components of the insulin-signaling pathway and the 40 insulin-like peptides in C. elegans may clarify the link between defective insulin signaling and AD and present novel treatment strategies for the disease.
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ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.