One is DNA damage, which can activate the apoptotic pathway via p53 phosphorylation.189 Another is represented by hypoxia and oxidative stress, which can also upregulate p53 protein levels.190 Concurrently and mechanistically, some upstream cascade proteins, including JNKs, p38, DAPK, ASK1, and Notch may also lead to p53 activation.31 All these factors stimulate p53 activity and lead to cellular apoptosis in ischemic stroke. The gene discussed is TP53; the disease is ischemic stroke.