15. Conclusion
In this paper, we have reviewed the research literature on the spike protein related processes that lead to the development of neurodegenerative disease, in the context of several recent papers reporting on the observed mechanisms of toxicity. We were initially motivated by the observation that COVID-19 patients often suffer from long-term sequelae that include cognitive impairment – so-called long-haul COVID disease. There is also a post-vaccination syndrome that strongly resembles long COVID.
Central to promotion of prion and prion-like disease is the induction of γ-secretase metabolism of the APP sequence, which, through BACE-1, yields the AIDC sequence, a highly potent transcriptional activator of the TP53 gene. This disease-prone metabolic state is induced through p38 MAPK activation in neurons. Therefore, the SARS-CoV-2 spike protein can be a re-enforcing toxicity factor, since it induces both p38 MAPK and JNK activation which subsequently will provide a surplus of activated p53. The activation of p53 is potentially further enforced through concurrent Wip1 deactivation by JNK-p53-induced miR-16 expression. Decreased degradation of p53 via the UPS and autophagy due to oxidative damage to the p62 promoter further enhances the risk to induction of neuronal apoptosis.
We propose that age-related impairments in autophagy may predispose towards increased risk to cognitive issues associated with the ability of the spike protein to behave as a prion-like protein, triggering misfolding of PrP and other amyloidogenic proteins. The spike protein has been shown to induce an inflammatory response in microglia, which can lead to oxidative stress and DNA damage. Through MAPK activation via TLR4 receptors, as well as JNK activation, the spike protein can be expected to suppress key phosphatases that normally would restore cellular homeostasis following p53 activation via MAPK. Sustained p53 phosphorylation in neurons can induce PrP conversion to PrPSC. The precipitation of misfolded PrP into fibrils causes a loss-of-function pathology, and subsequent catastrophic autophagy failure ultimately leads to programmed cell death (apoptosis) and resulting neurological symptoms and accelerated senescence.
Our work has important implications for public policy given the continued widespread application of COVID-19 vaccines. If the spike protein conceivably could contribute to future neurodegenerative diseases, then the risk-benefit calculation for mass indiscriminate vaccination should be re-examined. If the arguments presented here are found to be true, the vaccinated population has already been subjected to a great deal of harm.
Author Contributions: Conceptualization, A.K., G.N., S.S., and P.M., writing – original draft preparation, A.K., writing - review and editing, A.K., G.N., S.S., and P.M. All authors have read and agreed to the published version of the manuscript.
Funding: Stephanie Seneff was funded in part by Quanta Computers, Taiwan, under the auspices of the Qmulus project. The other three authors received no funding for this work.
Conflicts of Interest: The authors declare that they have no conflicts of interest.