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].