title: Experimental and potential future therapeutic approaches for HIV-1 associated dementia targeting receptors for chemokines, glutamate and erythropoietin.
abstract: Severe and debilitating neurological problems that include behavioral abnormalities, motor dysfunction and frank dementia can occur after infection with the human immunodeficiency virus-1 (HIV-1). Infected peripheral immune-competent cells, in particular macrophages, infiltrate the central nervous system (CNS) and provoke a neuropathological response involving all cell types in the brain. HIV-1 infection results in activation of chemokine receptors, inflammatory mediators, extracellular matrix-degrading enzymes and glutamate receptor-mediated excitotoxicity, all of which can trigger numerous downstream signaling pathways that result in disruption of neuronal and glial function. Despite many major improvements in the control of viral infection in the periphery, a truly effective therapy for HIV-1 associated dementia is currently not available. This review will discuss experimental and potentially future therapeutic strategies based on recently uncovered pathologic mechanisms contributing to neuronal damage induced by HIV-1.
authors.affiliation: Center for Neuroscience and Aging Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. mkaul@burnham.org
authors.forename: M
authors.initials: M
authors.lastname: Kaul
authors.forename: S A
authors.initials: SA
authors.lastname: Lipton
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D000818:Animals; D015497:HIV-1; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D009498:Neurotoxins / Q000378:metabolism; D019707:Receptors, Chemokine / Q000187:drug effects*; D017467:Receptors, Erythropoietin / Q000187:drug effects*; D017470:Receptors, Glutamate / Q000187:drug effects*
chemical_list: D018696:Neuroprotective Agents; D009498:Neurotoxins; D019707:Receptors, Chemokine; D017467:Receptors, Erythropoietin; D017470:Receptors, Glutamate