Recent Advances in the Molecular and Cellular Mechanisms of gp120-Mediated Neurotoxicity

Axonal degeneration and loss of synapses are often seen in different brain areas of people living with human immunodeficiency virus (HIV). Nevertheless, the underlying causes of the pathological alterations observed in these individuals are poorly comprehended, considering that HIV does not infect neurons. Experimental data have shown that viral proteins, including the envelope protein gp120, cause synaptic pathology followed by neuronal cell death. These neurotoxic effects on synapses could be the result of a variety of mechanisms that decrease synaptic plasticity. In this paper, we will briefly present new emerging concepts connected with the ability of gp120 to promote the degeneration of synapses by either directly damaging the axonal cytoskeleton and/or the indirect activation of the p75 neurotrophin receptor death domain in dendrites.