Journal
ANNALS OF MEDICINE
Volume 53, Issue 1, Pages 43-69Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/07853890.2020.1814962
Keywords
Microglia; Human immunodeficiency virus type 1 (HIV-1); HIV-1-associated neurocognitive disorders (HAND); Reactive oxygen species (ROS); Anti-retroviral therapy (ART); Chemokines (or chemotactic cytokines)
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Funding
- GAIN (Agencia Gallega de Innovacion) from the Conselleria de Cultura, Educacion e Ordenacion Universitaria [IN606B-2016/012]
- Conselleria de Economia, Emprego e Industria (Xunta de Galicia)
- Instituto de Salud Carlos III - European Regional Development Fund, A way to make Europe [PI18/01311]
- Ramon Cajal grant [RYC-2014-15246]
- Fundacion Tatiana Perez de Guzman el Bueno
- Instituto de Salud Carlos III, Ministerio de Economia y Competitividad [FIS P16/00405]
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The development of effective cART has reduced the death rate associated with HIV-1 infection, but over 50% of patients develop HAND. Microglia, as the primary cells infected by HIV-1 in CNS, contribute to neurotoxicity observed in HAND through inflammation and oxidative stress mechanisms. Understanding the activation of microglia and pathways involved in neuroinflammation is crucial for potential therapeutic targets in HAND treatment.
The development of effective combined anti-retroviral therapy (cART) led to a significant reduction in the death rate associated with human immunodeficiency virus type 1 (HIV-1) infection. However, recent studies indicate that considerably more than 50% of all HIV-1 infected patients develop HIV-1-associated neurocognitive disorder (HAND). Microglia are the foremost cells infected by HIV-1 in the central nervous system (CNS), and so, are also likely to contribute to the neurotoxicity observed in HAND. The activation of microglia induces the release of pro-inflammatory markers and altered secretion of cytokines, chemokines, secondary messengers, and reactive oxygen species (ROS) which activate signalling pathways that initiate neuroinflammation. In turn, ROS and inflammation also play critical roles in HAND. However, more efforts are required to understand the physiology of microglia and the processes involved in their activation in order to better understand the how HIV-1-infected microglia are involved in the development of HAND. In this review, we summarize the current state of knowledge about the involvement of oxidative stress mechanisms and role of HIV-induced ROS in the development of HAND. We also examine the academic literature regarding crucial HIV-1 pathogenicity factors implicated in neurotoxicity and inflammation in order to identify molecular pathways that could serve as potential therapeutic targets for treatment of this disease.KEY MESSAGES Neuroinflammation and excitotoxicity mechanisms are crucial in the pathogenesis of HAND. CNS infiltration by HIV-1 and immune cells through the blood brain barrier is a key process involved in the pathogenicity of HAND. Factors including calcium dysregulation and autophagy are the main challenges involved in HAND.
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