Figure 2. The SARS CoV-2 spike protein neurotoxicity dependence on age and inhibition of     autophagy. The ability to induce autophagy is age dependent. Autophagy is inhibited in part     through DNA damage to the sequestosome p62 promoter, caused by oxidative stress. The     activation of p38 MAPK and JNK pathways by the spike protein in nerve cells leads to BACE-1     activation and, through JNK-mediated Wip1 deactivation, increases activated (phosphorylated)     p53. The release of AIDC via APP metabolism further enhances TP53 transcriptional activation     and hence p53 expression. Free P53 can be further phosphorylated by ATM (being active through     JNK-dependent microRNA-16 Wip1 inhibition). The overall process leads to accumulation of     levels and expression of PrPC. Conformational alteration of PrPC to PrPSC induces the activation     of p38 MAPK, constituting the whole age-dependent process. Adopted from:     [10,13,73,91,94,97,106,107,110,112,122].