Search

The current use of combined antiretroviral therapy (cART) is leading to a significant decrease in deaths and comorbidities associated with human immunodeficiency virus type 1 (HIV-1) infection. Nonetheless, none of these therapies can extinguish the virus from the long-lived cellular reservoir, including microglia, thereby representing an important obstacle to curing HIV. Microglia are the foremost cells infected by HIV-1 in the central nervous system (CNS) and are believed to be involved in the development of HIV-1-associated neurocognitive disorder (HAND). At present, the pathological mechanisms contributing to HAND remain unclear, but evidence suggests that removing these infected cells from the brain, as well as obtaining a better understanding of the specific molecular mechanisms of HIV-1 latency in these cells, should help in the design of new strategies to prevent HAND and achieve a cure for these diseases. The goal of this review was to study the current state of knowledge of the neuropathology and research models of HAND containing virus susceptible target cells (microglial cells) and potential pharmacological treatment approaches under investigation.

Microglial cells exhibit properties akin to macrophages, thereby enabling them to support and protect the central nervous system environment. Aging induces alterations in microglial polarization, resulting in a shift toward a neurotoxic phenotype characterized by increased expression of pro-inflammatory markers. Dysregulation of microglial cells' regulatory pathways and interactions with neurons contribute to chronic activation and neurodegeneration. A better understanding of the involvement of microglia in neurodegenerative diseases such as Alzheimer's and Parkinson's is a critical topic for studying the role of inflammatory responses in disease progression. Furthermore, the metabolic changes in aged microglia, including the downregulation of oxidative phosphorylation, are discussed in this review. Understanding these mechanisms is crucial for developing better preventive and therapeutic strategies. [ABSTRACT FROM AUTHOR]