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Characterization of a novel host cellular factor involved in HIV-1 neuropathogenesis

Arumemi, Fortuna (2015) Characterization of a novel host cellular factor involved in HIV-1 neuropathogenesis. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

HIV-1 causes progressive neurological disorders collectively known as HIV-associated neurocognitive disorders (HAND). HAND is considered and umbrella term that encompasses three major stages: Asymptomatic neurocognitive impairment (ANI), mild/moderate neurocognitive disorder (MND), and HIV-associated dementia (HAD). The prevalence of HAND has increased despite the use of combined antiretroviral therapy (cART) and still affects 20 – 40% of HIV-1 infected individuals. The underlying cause of HAND observed in a particular set of subjects has not yet been fully elucidated nor have there been any ways to determine if an infected individual will eventually progress to HAND.
Previously we have shown that neurogranin (NRGN), a protein involved in the protein kinase C pathway and binds calmodulin (CaM) to decrease the threshold for long-term potentiation (LTP), which is involved in learning and memory is significantly downregulated in patients with high viral load at the mRNA level. With this in mind we theorize that there is a possible microRNA (miRNA) interaction with the 3’UTR of NRGN. We hypothesize that dysregulation of NRGN may be in part associated with development of HAND. To further understand the role of NRGN, we propose to delineate the role of NRGN and the mechanism(s) involved in HIV-1 induced degradation of NRGN.
The public health significance is in determining contributors to the degradation of cognition in HIV-1 infected individuals that progress to HAND, treatments can be developed to combat the effects on HIV-1 on proteins and cells pertinent to normal brain function.

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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Arumemi, Fortunafoa1@pitt.eduFOA1
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairAyyavoo, Velpandivelpandi@pitt.eduVELPANDI
Committee MemberMartinson, Jeremy Jjmartins@pitt.eduJMARTINS
Committee MemberMurphey-Corb, Michaelmcorb@pitt.eduMCORB
Date: 28 January 2015
Date Type: Publication
Defense Date: 6 October 2014
Approval Date: 28 January 2015
Submission Date: 21 July 2014
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 61
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: Neurogranin HIV-1 HAND miRNA Neuropathogenesis Western Blot
Date Deposited: 28 Jan 2015 15:11
Last Modified: 15 Nov 2016 14:22
URI: http://d-scholarship.pitt.edu/id/eprint/22444

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