Neuroprotective strategies for HIV-1 associated dementia

Huanyu Dou, Jeffrey D. Kingsley, R. Lee Mosley, Harris A. Gelbard, Howard E. Gendelman

Research output: Contribution to journalReview article

22 Scopus citations

Abstract

The human immunodeficiency virus-1 (HIV-1) commonly affects cognitive, behavioral and motor functions during the disease course. The neuropathogenesis of viral infection revolves around neurotoxins produced from infected and immune-activated mononuclear phagocytes (MP; perivascular macrophages and microglia). Direct infection of neurons occurs rarely, if at all. Neurologic disease arises in part as a consequence of MP metabolic dysfunction. Although the advent of highly active antiretroviral therapy (HAART) has attenuated the incidence and severity of neurologic disease, it, nonetheless, remains a common and disabling problem for those living with HIV-1 infection. Adjunctive therapies are currently designed to ameliorate clinical outcomes and are included in the therapeutic armamentarium. Antiinflammatory drugs that inhibit cytokines, chemokines and interferons linked to neurodegenerative processes can significantly ameliorate neuronal function. HIV-1 neurotoxins have the unique ability to up-regulate glycogen synthase kinase-3β (GSK-3β) activity that in turn elicits neuronal apoptosis. GSK-3β inhibitors are neuroprotective in animal models of Neuro AIDS. They are also currently in Phase 1 clinical trials designed for safety and tolerability in patients with HIV-1 infection. Neurotrophins are only beginning to be realized for their therapeutic potential in HIV-1 associated neurologic disease. This review article provides a broad overview of neuroprotective strategies for HIV-1 infection and details how such strategies act and may be implemented for treatment of human disease.

Original languageEnglish (US)
Pages (from-to)503-521
Number of pages19
JournalNeurotoxicity Research
Volume6
Issue number7-8
DOIs
StatePublished - Dec 1 2004

Keywords

  • HIV-1-associated dementia
  • Monocyte-derived macrophages
  • Neurodegenerative diseases
  • Neuronal injury
  • Neuroprotection
  • Neurotrophins

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

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