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.