TY - JOUR
T1 - Neuroprotective strategies for HIV-1 associated dementia
AU - Dou, Huanyu
AU - Kingsley, Jeffrey D.
AU - Mosley, R. Lee
AU - Gelbard, Harris A.
AU - Gendelman, Howard E.
N1 - Funding Information:
The project described was supported by NIH Grants: 1 T32 NS07488-01, 5 R37 NS36126-07, 5 R01 NS034239-10, 1 P01 NS43985-01A1, 5 P01NS31492-11, 5 R01 MH64570-03, P01 NS11766-28, 20 RR15635 from the COBRE Program of the National Center for Research Resources. The authors extend a special thanks to Ms. Robin Taylor for outstanding administrative, graphic and computer support. We acknowledgment the graphic assistance provided by William Wassom, Graphic Designer and Robin Taylor, Project Coordinator in the Department of Pharmacology, the University of Nebraska Medical Center in support and design of the cover illustration.
PY - 2004
Y1 - 2004
N2 - 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.
AB - 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.
KW - HIV-1-associated dementia
KW - Monocyte-derived macrophages
KW - Neurodegenerative diseases
KW - Neuronal injury
KW - Neuroprotection
KW - Neurotrophins
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U2 - 10.1007/BF03033447
DO - 10.1007/BF03033447
M3 - Review article
C2 - 15639783
AN - SCOPUS:15844371968
SN - 1029-8428
VL - 6
SP - 503
EP - 521
JO - Neurotoxicity Research
JF - Neurotoxicity Research
IS - 7-8
ER -