Figure 2

Mechanisms of gp120 neurotoxicity. (1) gp120 can bind to the NMDA receptor and lead to excessive opening of NMDAR-gated cation channels, allowing the influx of calcium ions to toxic levels [54]. (2) gp120 can directly bind to either CCR5 or CXCR4, activating an p38-MAPK mediated signaling cascade that leads to neuronal apoptosis [56]. The gp120-CXCR4 binding also up-regulates the expression of the nicotinic receptor α7, which increases cellular permeability to [Ca²⁺] influx and contributes to cell death [61].