HIV-associated neurotoxicity and cognitive decline: Therapeutic implications

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Abstract

As our understanding of changes to the neurological system has improved, it has become clear that patients who have contracted human immunodeficiency virus type 1 (HIV-1) can potentially suffer from a cascade of neurological issues, including neuropathy, dementia, and declining cognitive function. The progression from mild to severe symptoms tends to affect motor function, followed by cognitive changes. Central nervous system deficits that are observed as the disease progresses have been reported as most severe in later-stage HIV infection. Examining the full spectrum of neuronal damage, generalized cortical atrophy is a common hallmark, resulting in the death of multiple classes of neurons. With antiretroviral therapy (ART), we can partially control disease progression, slowing the onset of the most severe symptoms such as, reducing viral load in the brain, and developing HIV-associated dementia (HAD). HAD is a severe and debilitating outcome from HIV-related neuropathologies. HIV neurotoxicity can be direct (action directly on the neuron) or indirect (actions off-site that affect normal neuronal function). There are two critical HIV-associated proteins, Tat and gp120, which bear responsibility for many of the neuropathologies associated with HAD and HIV-associated neurocognitive disorder (HAND). A cascade of systems is involved in HIV-related neurotoxicity, and determining a critical point where therapeutic strategies can be employed is of the utmost importance. This review will provide an overview of the existing hypotheses on HIV-neurotoxicity and the potential for the development of therapeutics to aid in the treatment of HIV-related nervous system dysfunction.

Original languageEnglish
Article number108047
JournalPharmacology and Therapeutics
Volume234
DOIs
StateAccepted/In press - 2021

Keywords

  • Apoptosis
  • gp120
  • NeuroAIDS
  • Oxidative stress
  • Tat

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