HIV-associated neurocognitive disorder: pathogenesis and therapeutic opportunities.
Human immunodeficiency virus type 1 (HIV) infection presently affects more that 40 million people worldwide, and is associated with central nervous system (CNS) disruption in at least 30% of infected individuals. The use of highly active antiretroviral therapy has lessened the incidence, but not the prevalence of mild impairment of higher cognitive and cortical functions (HIV-associated neurocognitive disorders) as well as substantially reduced a more severe form dementia (HIV-associated dementia). Furthermore, improving neurological outcomes will require novel, adjunctive therapies that are targeted towards mechanisms of HIV-induced neurodegeneration. Identifying such molecular and pharmacological targets requires an understanding of the events preceding irreversible neuronal damage in the CNS, such as actions of neurotoxins (HIV proteins and cellular factors), disruption of ion channel properties, synaptic damage, and loss of adult neurogenesis. By considering the specific mechanisms and consequences of HIV neuropathogenesis, unified approaches for neuroprotection will likely emerge using a tailored, combined, and non-invasive approach.
Lindl
Kathryn A
KA
Department of Pathology, School of Dental Medicine, University of Pennsylvania, 240 S. 40th St, Room 312 Levy Building, Philadelphia, PA 19104-6030, USA.
Marks
David R
DR
Kolson
Dennis L
DL
Jordan-Sciutto
Kelly L
KL
D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use; D001921:Brain / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D008559:Memantine / Q000627:therapeutic use; D008911:Minocycline / Q000627:therapeutic use; D015213:Neuroimmunomodulation / Q000276:immunology / Q000502:physiology; D012642:Selegiline / Q000627:therapeutic use
D019380:Anti-HIV Agents; D012642:Selegiline; D008911:Minocycline; D008559:Memantine
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