Furthermore, in ovariectomized APP/PS1 mice (an AD animal model), systemic administration of E2 (17β-estradiol) or the estrogen receptor α (ERα) agonist propylpyrazoletriol (PPT) increased ubiquitination of Cav1.2 in the brain, reversed elevated levels of Cav1.2 protein, and improved cognitive functioning. The gene discussed is ESR1; the disease is Alzheimer disease.