Neuronal homeostasis is an essential process to protect neurons from over/under-stimulation driven from systematic changes such as synapsis plasticity or tissue damage. Functional stability in neurons relays on the homeostatic plasticity that its disturbance causes irreversible injuries. Hence, a large body of studies elaborated to investigate the underlying mechanism for changes in synaptic connectivity and neuronal function. HIV-1 Tat (Transactivation of transcription), is a well-established neurotoxic protein, released by HIV-1 infected cells in the brain and disturbs neuronal homeostasis. The effects of Tat have been addressed in numerous studies investigating the molecular events associated with neuronal cell survival and death. The emergence of lncRNAs as critical players in disease etiology placed them in the spotlight to study pathogenesis of human diseases. Due to its capacity to modulate host transcriptome, HIV-1 Tat protein has been subjected to increasing genome-wide examinations. This study showed that exposing primary rat neurons to Tat resulted in the up-regulation of an uncharacterized long-non-coding RNA (lncRNA), LOC102549805 (lncRNA-U1). Evidence exists that increased expression of lncRNA-U1 in neurons disrupts bioenergetic pathways by dysregulating homeostasis of Ca2+, mitigating mitochondrial oxygen reduction, and decreasing ATP production leading to mitochondrial impairment in neurons. These changes were associated with imbalances in autophagy and apoptosis pathways via the Tat-mediated lncRNA-U1 induction.
Additionally, this study showed the ability of Tat to modulate the expression of the neuropeptide B/W receptor 1 (NPBWR1) gene via the up-regulation of lncRNA-U1. Collectively, my results identified the Tat-mediated lncRNA-U1 elevation disturbs neuronal homeostasis. Our observations of lncRNA-U1 knock-down experiments indicated the novel lncRNA LOC102549805 (U1) as a viable therapeutic target to prevent HIV-1 Tat neurotoxicity. / Biology
| Identifer | oai:union.ndltd.org:TEMPLE/oai:scholarshare.temple.edu:20.500.12613/348 |
| Date | January 2020 |
| Creators | Torkzaban, Bahareh, 0000-0003-2757-0751 |
| Contributors | Amini, Shohreh, Khalili, Kamel, 1951-, Waring, Richard B., Yang, Weidong, Dr., Nonnemacher, Michael R. |
| Publisher | Temple University. Libraries |
| Source Sets | Temple University |
| Language | English |
| Detected Language | English |
| Type | Thesis/Dissertation, Text |
| Format | 110 pages |
| Rights | IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available., http://rightsstatements.org/vocab/InC/1.0/ |
| Relation | http://dx.doi.org/10.34944/dspace/332, Theses and Dissertations |
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