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Current HIV Research
ISSN (Print): 1570-162X
ISSN (Online): 1873-4251
VOLUME: 4
ISSUE: 3
DOI: 10.2174/157016206777709384      Price:  $58









Mechanisms of Neuronal Injury and Death in HIV-1 Associated Dementia

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Author(s): Marcus Kaul and Stuart A. Lipton
Pages 307-318 (12)
Abstract:
Infection with the human immunodeficiency virus-1 (HIV-1) and acquired immunodeficiency syndrome (AIDS) remain a persistent and even growing health problem worldwide. Besides its detrimental systemic effects on the immune system, HIV-1 seems to enter the brain very soon after peripheral infection and can induce severe and debilitating neurological problems that include behavioral abnormalities, motor dysfunction and frank dementia. Infected peripheral immune cells, in particular macrophages, appear to infiltrate the CNS and provoke a neuropathological response involving all cell types in the brain. Both viral and host factors, such as the viral strain and the response of the hosts immune system, strongly influence the course of HIV-1 disease. Moreover, HIV-1-dependent disease processes in the periphery have a substantial effect on the pathology developing in the central nervous system (CNS), although the brain eventually harbors a distinctive viral population of its own. In the CNS, HIV-1 also initiates activation of chemokine receptors, inflammatory mediators, extracellular matrix-degrading enzymes and glutamate receptor-mediated excitotoxicity, all of which can activate numerous downstream signaling pathways and disturb neuronal and glial function. Although there have been substantial improvements in the control of viral infection in the periphery, an effective therapy for HIV-1 associated dementia (HAD) is still not in sight. This article will review recently identified injurious mechanisms potentially contributing to neuronal death in association with HIV-1 disease and discuss recent and prospective approaches for therapy and prevention of HAD.
Keywords:
HIV-1, neurotoxicity, apoptosis, neurodegeneration, dementia
Affiliation:
Center for Neuroscience andAging Research, Burnham Institute for Medical Research, 10901 NorthTorrey Pines Road, La Jolla, CA 92037, USA.