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Theses and Dissertations

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Browsing Theses and Dissertations by Author "Alsulami, Abdullatif M., author"

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    Skn-1, Nrf homolog, mediates cannabidiol cellular stress responsive effects in Caenorhabditis elegans
    (Colorado State University. Libraries, 2023) Alsulami, Abdullatif M., author; Moreno, Julie, advisor; McGrath, Stephanie, committee member; LaRocca, Tom, committee member; Arnold, Olivia, committee member
    Alzheimer's disease (AD) is a neurodegenerative disease that is affecting an increasing number of the aged population worldwide. AD is characterized by the accumulation of amyloid beta (Aβ) and tau hyperphosphorylation along with a failure in redox homeostasis. The hallmarks of neurodegenerative diseases include the increased generation of reactive oxygen species (ROS) which is tightly controlled by an antioxidant defense mechanism under physiological conditions. This research aimed to utilize various strains of the model organism C. elegans to understand the mechanism of cannabidiol at the cellular level in stressed models. The SKN-1 gene, the Nrf homolog in C. elegans, encodes for three different isoforms, skn-1a, skn-1b, and c. Skn-1b/c, which plays a role in oxidative stress, is negatively regulated by the repressor WDR-23. In C. elegans, skn-1a plays a role in proteotoxic stress through upregulation proteosome subunits and is negatively regulated by the abundance of proteosome complex protein. Results show that 10μM of CBD was able to activate isoforms of skn-1, skn-1a and skn-1b/c. The ROS scavenging activity of CBD was dependent on the presence of skn-1b/c. Furthermore, CBD's protective effects under proteotoxic stress were diminished in the absence of skn-1a. Further investigation will be conducted to identify the role of skn-1 in CBD's reduction of Aβ plaques.