Mechanisms of cytomegalovirus regulation of neurodegenerative markers
| dc.contributor.advisor | Hanson, Laura K. | |
| dc.contributor.advisor | Hynds, DiAnna L. | |
| dc.creator | Mody, Prapti | |
| dc.date.accessioned | 2019-11-13T15:01:17Z | |
| dc.date.available | 2019-11-13T15:01:17Z | |
| dc.date.created | 2019-08 | |
| dc.date.issued | 9/9/2019 | |
| dc.date.submitted | 19-Aug | |
| dc.date.updated | 2019-11-13T15:01:18Z | |
| dc.description.abstract | Alzheimer’s disease (AD) manifests with loss of neurons associated with intercellular amyloid plaques made up of amyloid beta peptides (Aβ) and intracellular neurofibrillary tangles of hyperphosphorylated tau proteins. Normally, Aβ peptides function as cell signaling molecules and can mediate antimicrobial activity. Tau is one of the microtubule stabilizing proteins in cells and its expression and post-translational modifications depend upon cell type and cell age. Despite testing many therapeutics designed to target abnormal amyloid or tau, there is no sustained treatment. Current research is therefore focused on early steps in production of dysfunctional amyloid and tau11, however, there are relatively few strong established models for these studies. Previous researchers have shown that some herpesvirus infections can alter amyloid and tau in ways similar to that seen in AD. There is clinical correlation between herpesvirus infection and higher risk of AD. Herpes simplex virus 1 can interact with amyloid precursor protein (APP) and affect tau v hyperphosphorylation. Based on these findings, we hypothesized that MCMV infection could be a useful model if it similarly impacted AD markers. We found that APP was upregulated in MCMV-infected fibroblasts and viral late gene products were required. Levels of processing enzymes (secretases) and one cleavage product (Aβ42) were unchanged. The activity of β-secretase was not increased. There was no similar APP induction in RCN. Thus, CMV may have cell-type or species-based differences for effects on the amyloid pathway. Levels of total tau and tau phosphorylated at S396 were increased in MCMV-infected fibroblasts and neurons. This also required viral late gene products. There was no change in tau phosphorylation at S202 or GSK3β levels. We used lithium chloride (LiCl) to inhibit activity of GSK3. Although MCMV infection was inhibited, the banding patterns for tau and phospho-tau (S396) exhibited minor alterations when LiCl was added at the time that changes started. Thus, other kinases are more likely important. We have confirmed that MCMV can induce AD markers. This is useful for using MCMV infection in AD animal models for elucidation of early steps, promising for testing novel preventives for these changes, and for developing novel antivirals. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | https://hdl.handle.net/11274/11983 | |
| dc.language.iso | en | |
| dc.subject | Cytomegalovirus | |
| dc.subject | Alzheimer's disease | |
| dc.subject | Herpes virus | |
| dc.subject | Neurodegenerative disease | |
| dc.subject | Neurodegeneration | |
| dc.title | Mechanisms of cytomegalovirus regulation of neurodegenerative markers | |
| dc.type | Thesis | |
| dc.type.material | text | |
| thesis.degree.department | Biology | |
| thesis.degree.discipline | Molecular Biology | |
| thesis.degree.grantor | Texas Woman's University | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Doctor of Philosophy |
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