CXCL8作为潜在治疗HIV相关的神经认知障碍的靶点

Title:CXCL8 as a Potential Therapeutic Target for HIV-Associated Neurocognitive Disorders

Volume: 17 Issue: 1

Author(s): Manmeet K. Mamik and Anuja Ghorpade

Affiliation:

关键词: 趋化因子，CXCL8，CXCR1/CXCR2，HIV-1，神经退行性疾病，神经保护作用。

摘要: Chemokine CXCL8 is a low molecular weight neutrophil chemoattractant implicated in various neurodegenerative disorders including Alzheimer's disease and stroke. Increased expression of CXCL8 has been reported in serum, plasma and brain of human immunodeficiency virus (HIV)-1 infected individuals with neurocognitive impairment, indicating its role in neuroinflammation associated with HIV-1 infection of the brain. Since chemokines are critical in eliciting immune responses in the central nervous system (CNS), CXCL8 is of particular importance for being one of the first chemokines described in the brain. Activation of astrocytes and microglia by HIV-1 and virus associated proteins results in production of this chemokine in the brain microenvironment. Consequently, CXCL8 exerts its effect on target cells via Gprotein coupled receptors CXCR1 and CXCR2. Neutrophils are the main target cells for CXCL8; however, microglia and neurons also express CXCR1/CXCR2 and therefore are important targets for CXCL8-mediated crosstalk. The objective of this review is to focus on CXCL8 production, signaling and regulation in neuronal and glial cells in response to HIV-1 infection. We highlight the role of HIV-1 secreted proteins such as trans-activator of transcription, envelope glycoprotein, negative regulatory factor and viral protein r in the regulation of CXCL8. We discuss dual role of CXCL8 in neurodegeneration as well as neuroprotection in the CNS. Thus, targeting CXCL8 through the development of CXCR1/CXCR2-based therapeutic strategies to either selectively agonize or antagonize receptors may be able to selectively promote neuroprotective and anti-inflammatory outcomes, leading to significant clinical applications in many neuroinflammatory CNS diseases, including HIV-associated neurocognitive disorders.

Cite this article as:

Manmeet K. Mamik and Anuja Ghorpade , CXCL8 as a Potential Therapeutic Target for HIV-Associated Neurocognitive Disorders, Current Drug Targets 2016; 17 (1) . https://dx.doi.org/10.2174/1389450116666150626124544