Neurotrophic factors and neuroAIDS: A lesson from brain-derived neurotrophic factor

Abstract

Human immunodeficiency virus type 1 (HIV) causes mild or severe neurological problems, termed HIV-associated neurocognitive disorder (HAND), even when HIV patients receive antiretroviral therapy. Thus, novel adjunctive therapies are necessary to reduce or abolish the neurotoxic effect of HIV. However, new therapies require a better understanding of the molecular and cellular mechanisms of HIV-induced neurotoxicity. HAND subjects are characterized by being profoundly depressed, and they experience deficits in memory, learning, and movements. These deficits resemble those occurring in premature brain aging. Thus, it appears that HIV diminishes neuronal survival, along with reduced neuronal connections. These two phenomena should not occur in the adult brain when synaptic plasticity is promoted by neurotrophic factors. In particular, synaptic plasticity is enhanced by brain-derived neurotrophic factor (BDNF), a potent neurotrophic factor that is present in abundance in the adult synapses. This chapter will outline experimental evidence as well as present emerging concepts for the use of BDNF as an adjunct therapy to prevent HIV-mediated neuronal degeneration and restore the loss of synaptic connections.