HIV-1 gp120 protein promotes HAND through the calcineurin pathway activation.

Autor: Shrestha J; Molecular Studies of Neurodegenerative Diseases Lab; FELS Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine - Temple University Philadelphia, PA 19140, USA. Electronic address: jenny.shrestha@bms.com., Santerre M; Molecular Studies of Neurodegenerative Diseases Lab; FELS Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine - Temple University Philadelphia, PA 19140, USA., Allen CN; Molecular Studies of Neurodegenerative Diseases Lab; FELS Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine - Temple University Philadelphia, PA 19140, USA., Arjona SP; Molecular Studies of Neurodegenerative Diseases Lab; FELS Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine - Temple University Philadelphia, PA 19140, USA., Hooper R; FELS Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine - Temple University Philadelphia, PA 19140, USA., Mukerjee R; Molecular Studies of Neurodegenerative Diseases Lab; FELS Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine - Temple University Philadelphia, PA 19140, USA., Kaul M; Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA; Department of Psychiatry, UCSD, San Diego, CA, USA; Division of Biomedical Sciences, School of Medicine, UCR, Riverside, CA, USA., Shcherbik N; Department for Cell Biology and Neuroscience, School of Osteopathic Medicine, Rowan University, 2 Medical Center Drive, Stratford, NJ 08084, USA., Soboloff J; FELS Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine - Temple University Philadelphia, PA 19140, USA; Department of Cancer and Cellular Biology, Lewis Katz School of Medicine - Temple University Philadelphia, PA 19140, USA., Sawaya BE; Molecular Studies of Neurodegenerative Diseases Lab; FELS Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine - Temple University Philadelphia, PA 19140, USA; Department of Cancer and Cellular Biology, Lewis Katz School of Medicine - Temple University Philadelphia, PA 19140, USA. Electronic address: sawaya@temple.edu.
Jazyk: angličtina
Zdroj: Mitochondrion [Mitochondrion] 2023 May; Vol. 70, pp. 31-40. Date of Electronic Publication: 2023 Mar 15.
DOI: 10.1016/j.mito.2023.03.003
Abstrakt: For over two decades, highly active antiretroviral therapy (HAART) was able to help prolong the life expectancy of people living with HIV-1 (PLWH) and eliminate the virus to an undetectable level. However, an increased prevalence of HIV- associated neurocognitive disorders (HAND) was observed. These symptoms range from neuronal dysfunction to cell death. Among the markers of neuronal deregulation, we cite the alteration of synaptic plasticity and neuronal communications. Clinically, these dysfunctions led to neurocognitive disorders such as learning alteration and loss of spatial memory, which promote premature brain aging even in HAART-treated patients. In support of these observations, we showed that the gp120 protein deregulates miR-499-5p and its downstream target, the calcineurin (CaN) protein. The gp120 protein also promotes the accumulation of calcium (Ca 2+ ) and reactive oxygen species (ROS) inside the neurons leading to the activation of CaN and the inhibition of miR-499-5p. gp120 protein also caused mitochondrial fragmentation and changes in shape and size. The use of mimic miR-499 restored mitochondrial functions, appearance, and size. These results demonstrated the additional effect of the gp120 protein on neurons through the miR-499-5p/calcineurin pathway.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)
Databáze: MEDLINE
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