FIGURE 8.

Model for the mechanisms of glutamate-induced DNA damage and repair in neurons. Activation of glutamate receptors results in Ca²⁺ influx which, in turn, induces mitochondrial superoxide production and opening of PTP in the mitochondrial membranes. The superoxide or related reactive oxygen species then cause nuclear DNA damage. The DNA damage can be prevented by chelating intracellular Ca²⁺, by removing mitochondrial superoxide and blocking the PTP. Glutamate-induced Ca²⁺ influx also triggers the activation of CaMK and CREB resulting in increased expression of APE1 and repair of the damaged DNA.