Figure 3. Schematic diagram of the underlying mechanism of neuronal cell death by oxidative glutamate toxicity. Glutamate up-regulates GM3 levels, which in turn leads to massive ROS production and Ca²⁺ influx in neuronal cell death. 12-LOX is translocated to GEM in a GM3-dependent manner. This pathway can be disrupted by the pharmacological inhibition of GM3 synthesis or by silencing the GM3 synthase gene.