In addition, berberine improves endoplasmic reticulum stress and, therefore, attenuates cognitive deficits since endoplasmic reticulum stress is central to signaling by the mechanism of tau protein phosphorylation by hyperactivation of glycogen synthase kinase 3β (GSK 3β) and phosphorylation of eukaryotic translation initiation factor-2α (eIF2α) by activation of PRKR-like endoplasmic reticulum kinase (PERK). The gene discussed is EIF2A; the disease is Cognitive impairment.