HIV-Associated Neurocognitive Disorder: A Look into Cellular and Molecular Pathology

被引:1
|
作者
Thompson, Landon John-Patrick [1 ]
Genovese, Jessica [1 ]
Hong, Zhenzi [1 ]
Singh, Meera Vir [2 ]
Singh, Vir Bahadur [1 ]
机构
[1] Albany Coll Pharm & Hlth Sci, Dept Life Sci, Albany, NY 12208 USA
[2] Univ Rochester, Dept Neurol, Rochester, NY 14642 USA
基金
美国国家卫生研究院;
关键词
HIV; HAND; neuroinflammation; microglia; latency; platelet; HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; RNA-POLYMERASE-II; NF-KAPPA-B; BLOOD-BRAIN-BARRIER; PLATELET-MONOCYTE COMPLEXES; NEGATIVE ELONGATION-FACTOR; COGNITIVE PERFORMANCE; WHITE-MATTER; HEPATITIS-C;
D O I
10.3390/ijms25094697
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Despite combined antiretroviral therapy (cART) limiting HIV replication to undetectable levels in the blood, people living with HIV continue to experience HIV-associated neurocognitive disorder (HAND). HAND is associated with neurocognitive impairment, including motor impairment, and memory loss. HIV has been detected in the brain within 8 days of estimated exposure and the mechanisms for this early entry are being actively studied. Once having entered into the central nervous system (CNS), HIV degrades the blood-brain barrier through the production of its gp120 and Tat proteins. These proteins are directly toxic to endothelial cells and neurons, and propagate inflammatory cytokines by the activation of immune cells and dysregulation of tight junction proteins. The BBB breakdown is associated with the progression of neurocognitive disease. One of the main hurdles for treatment for HAND is the latent pool of cells, which are insensitive to cART and prolong inflammation by harboring the provirus in long-lived cells that can reactivate, causing damage. Multiple strategies are being studied to combat the latent pool and HAND; however, clinically, these approaches have been insufficient and require further revisions. The goal of this paper is to aggregate the known mechanisms and challenges associated with HAND.
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页数:20
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