Fig. 2.

σ-1R-mediated neuroprotection. a In the absence of σ-1R activation, the increased influx of Ca²⁺ through GluN2B-containing NMDARs can trigger neurotoxicity and neurodegeneration by increasing the activation of nNOS (eventually NO species) that is attached to PSD-95. b Recent investigations have demonstrated that the activation of σ-1Rs leads to diminution of interactions between GluN2B subunits and PSD-95 as well as PSD-95 and nNOS (represented as a decrease in size). Reducing the interactions between proteins that can generate toxic species may be one of the underlying mechanisms of σ-1R-mediated neuroprotection via reduced neurotoxicity and neurodegeneration [22,25,26,27].