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Neuroprotective micro RNAs as a potential therapeutic for HIV-associated neurocognitive disorders

Suresh Babu, Naveen (2021) Neuroprotective micro RNAs as a potential therapeutic for HIV-associated neurocognitive disorders. Master's Thesis, University of Pittsburgh. (Unpublished)

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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
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Suresh Babu, Naveennas267@pitt.edunas267
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairAyyavoo, Velpandivelpandi@pitt.eduvelpandi
Committee MemberMartinson, Jeremyjmartins@pitt.edujmartins
Committee MemberPeter Di, Yuanpupeterdi@pitt.edupeterdi
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: Graduate 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 2021 13:54
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) [Currently Displayed]

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