Suresh Babu, Naveen
(2021)
Neuroprotective micro RNAs as a potential therapeutic for HIV-associated neurocognitive disorders.
Master's Thesis, University of Pittsburgh.
(Unpublished)
This is the latest version of this item.
Abstract
Around 75 million people have been infected with the Human Immunodeficiency Virus-1 (HIV-1) since the inception of the epidemic, and it is estimated that nearly 38 million people are now living with the virus. As many as 50% of these individuals develop HIV-associated neurocognitive disorders (HAND) despite being on antiretroviral therapy. This process involves progressive loss of synaptic plasticity and dendritic morphology leading to motor problems, loss of memory, speech impairment and overall reduced quality of life. The constellation of symptoms associated with HAND seems to arise from virus-associated immune activation involving the microglia and macrophages in the CNS niche. Previous findings from our laboratory have indicated the differential expression of certain miRNAs in the PBMCs HIV+ HAND+ patients. Furthermore, preliminary data have suggested that these endogenous micro RNAs might have therapeutic potential in treating HAND. Based on these observations, we hypothesized that overexpression of these miRNAs in microglia might abate HIV-mediated inflammation and subsequent damage due to it. Results indicate that overexpression of miR-20a and miR-106b through lentiviral transduction reduced pro-inflammatory cytokine expression in macrophages and microglia cell lines. My project aims at corroborating this phenomenon in immortalized HMC3 microglia cell line and develop 3D brain organoids which would be useful to establish the physiological relevance of our hypothesis. If successful, these miRNAs would eventually lead to a new class of antiretroviral drugs to curb infection, inflammation, and neurodegeneration due to HIV-1.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
11 May 2021 |
| Date Type: |
Publication |
| Defense Date: |
12 April 2021 |
| Approval Date: |
11 May 2021 |
| Submission Date: |
20 April 2021 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
100 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Infectious Diseases and Microbiology |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
HIV, HAND, miRNA, micro RNA, neurobiology |
| Date Deposited: |
11 May 2021 13:54 |
| Last Modified: |
11 May 2023 05:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/40721 |
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Neuroprotective micro RNAs as a potential therapeutic for HIV-associated neurocognitive disorders. (deposited 11 May 2021 13:54)
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