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Molecular mechanisms of HIV-1 associated neurodegeneration

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Abstract

Since identification of the human immunodeficiency virus-1 (HIV-1), numerous studies suggest a link between neurological impairments, in particular dementia, with acquired immunodeficiency syndrome (AIDS) with alarming occurrence worldwide. Approximately, 60% of HIV-infected people show some form of neurological impairment, and neuropathological changes are found in 90% of autopsied cases. Approximately 30% of untreated HIV-infected persons may develop dementia. The mechanisms behind these pathological changes are still not understood. Mounting data obtained byin vivo andin vitro experiments suggest that neuronal apoptosis is a major feature of HIV associated dementia (HAD), which can occur in the absence of direct infection of neurons. The major pathway of neuronal apoptosis occurs indirectly through release of neurotoxins by activated cells in the central nervous system (CNS) involving the induction of excitotoxicity and oxidative stress. In addition a direct mechanism induced by viral proteins in the pathogenesis of HAD may also play a role. This review focuses on the molecular mechanisms of HIV-associated dementia and possible therapeutic strategies.

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Abbreviations

AIDS:

Acquired immunodeficiency syndrome

BMVEC:

brain microvascular endothelial cells

CNS:

central nervous system

CSF:

cerebrospinal fluid

FKN:

fractalkine

HAART:

highly active antiretroviral therapy

HAD:

HIV associated dementia

LTR:

lony terminal repeat

PAF:

platelet activating factor

PGE2 :

prostaglandin E2

ROS:

reactive oxygen species

SIV:

semian immunodeficiency virus

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    Hakan Ozdener

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Ozdener, H. Molecular mechanisms of HIV-1 associated neurodegeneration. J. Biosci. 30, 391–405 (2005). https://doi.org/10.1007/BF02703676

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