Pharmacological Regulation of Protein Translation in Fragile X Syndrome
| dc.contributor.advisor | Dussor, Gregory | |
| dc.contributor.advisor | Price, Theodore | |
| dc.contributor.committeeMember | Delk, Nikki | |
| dc.contributor.committeeMember | Palmer, Kelli | |
| dc.contributor.committeeMember | Sapkota, Darshan | |
| dc.creator | Shukla, Tarjani | |
| dc.date.accessioned | 2023-05-31T14:27:08Z | |
| dc.date.available | 2023-05-31T14:27:08Z | |
| dc.date.created | 2022-12 | |
| dc.date.issued | 2022-12-01T06:00:00.000Z | |
| dc.date.submitted | December 2022 | |
| dc.date.updated | 2023-05-31T14:27:09Z | |
| dc.description.abstract | The behavioral hallmarks of Autism Spectrum Disorder (ASD) are driven by molecular mechanisms that remain largely unknown. One model of ASD involves the deletion of the Fmr1 gene. Mutations in Fmr1 cause Fragile X Syndrome (FXS) and are the most common monogenetic source of intellectual disability in humans. The Fmr1 gene encodes for Fragile X Mental Retardation Protein (FMRP). FMRP is a conserved RNA-binding protein that binds the ribosome and attenuates translation. Loss of FMRP results in aberrant protein translation. This genetic lesion results in widespread cognitive deficiencies, specifically with learning, memory, and social interaction. A deeper understanding of the mechanism driving FMRP-dependent synaptic plasticity enables identification of highly specific therapeutics that ameliorate core neurological deficits associated with the disorder. In FXS, eIF4E is hyperphosphorylated and has emerged as a therapeutic target. Yet, specific inhibitors of Mitogen-Activated Protein Kinase Interacting Protein Kinase (MNK) have not been examined in the context of Fmr1 -/y mice. The goal of this research is to understand if compensation of FMRP loss can be achieved through manipulation of translation by the MNK-eIF4E regulatory axis. The results of this dissertation outline the viability of a novel therapeutic for the reversal of behaviors associated with Fragile X Syndrome, for which there are no FDA-approved treatments. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | ||
| dc.identifier.uri | https://hdl.handle.net/10735.1/9716 | |
| dc.language.iso | en | |
| dc.subject | Biology, Neuroscience | |
| dc.subject | Biology, Molecular | |
| dc.title | Pharmacological Regulation of Protein Translation in Fragile X Syndrome | |
| dc.type | Thesis | |
| dc.type.material | text | |
| thesis.degree.college | School of Natural Sciences and Mathematics | |
| thesis.degree.department | Biology - Molecular and Cell Biology | |
| thesis.degree.grantor | The University of Texas at Dallas | |
| thesis.degree.name | PHD |
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