Validation of SUMO-2 involvement in response to neuronal stressors has recently emerged in several systems, including APP overexpression in AD mice (McMillan et al., 2011), transient cerebral ischemia in brains of ground squirrels (Lee et al., 2012), and transient ischemia in cells (Yang et al., 2012), in some cases, promoting a neuroprotective response to ischemic stress (Datwyler et al., 2011). This evidence concerns the gene APP and Alzheimer disease.