FIG. 2. Schematic depicting the role of ROS in the molecular mechanisms underlying cognition.

(A) Low concentrations of ROS are required for signaling, synaptic plasticity, and memory formation; however, as the concentration of ROS increases, their function switches from a signaling molecule to an inhibitory or even toxic molecule. (B) On the left: superoxide and H₂O₂ activate protein kinase C (PKC) and extracellular-signal regulated kinase (ERK) and oxidize neurogranin (NG), which then releases calmodulin, resulting in the activation of calcium/calmodulin-dependent protein kinase II (CaMKII). On the right: superoxide and H₂O₂ also inhibit calcineurin (a.k.a. protein phosphatase 2B, PP2B). Activation of PKC, ERK, and CaMKII promote LTP, whereas the activity of PP2B tends to block LTP; thus activation of PKC, ERK, and CaMKII, along with the inhibition PP2B are all plausible, redox-sensitive, mechanisms by which ROS could promote synaptic plasticity in a concentration-dependent and cellular signaling state-dependent manner.