Protein aggregates can be transmitted from one cell to another through at least three distinct mechanisms: tunneling nanotubes, secretion as naked aggregates, or packaging up into extracellular vesicles such as exosomes. Furthermore, researchers are finding that the TAR-DNA binding protein of 43 kDa (TDP-43), a protein that misfolds in association with ALS, forms aggregates that propagate between cells in a prion-like manner. Both Tau and α-synuclein have been characterized as amyloidogenic. These proteins, which are termed amyloidogenic, have also been labeled as "prion-like," and their spread may also have properties that overlap with the classic stricter definition of the prion protein (PrP). It is increasingly becoming apparent that there is a generalization of prion diseases that can encompass neurodegenerative diseases such as Alzheimer's, Parkinson's disease, and amyotrophic lateral sclerosis (ALS), which are also associated with misfolded proteins that accumulate in plaques and Lewy bodies. In contrast, the insoluble plaque may even be protective in that it results in the clearing of the soluble oligomers. It is now generally recognized that an intermediate soluble oligomeric form of the protein is the toxic agent. Disease propagation occurs through an autocatalytic process whereby external misfolded prion proteins (PrP SC) act as an infectious agent to facilitate misfolding of the same protein expressed in neurons. In common nomenclature, the naturally folded form of the prion protein is referred to as PrP C, whereas the misfolded form is called PrP SC (for "scrapie"). Fatal familial insomnia (FFI) is a rare fatal genetic disease caused by certain mutations in the prion protein. The primary human prion disease is known as Creutzfeldt-Jakob disease (CJD), and it is always fatal. They include the familiar mad cow disease (bovine spongiform encephalopathy), scrapie in sheep, and chronic wasting disease (CWD) in deer. They are caused by 'proteinaceous infectious particles,' which can facilitate disease spread in the absence of a classical infection by a living organism. Prion diseases, also known as transmissible spongiform encephalopathies (TSEs), are a group of rare, consistently fatal brain diseases affecting animals and humans. Finally, we describe the implications of our findings for the general public, and we briefly discuss public health recommendations we feel need urgent consideration.Īn earlier version of this article was previously posted to the Authorea preprint server on August 16, 2022. We also acknowledge that the evidence we usher in, while grounded in the research literature, is currently largely circumstantial, not direct. We acknowledge that the chain of pathological events described throughout this paper is only hypothetical and not yet verified. We note with an optimism an apparent loss of prion-like properties among the current Omicron variants. We explain why these prion-like characteristics are more relevant to vaccine-related mRNA-induced spike proteins than natural infection with SARS-CoV-2. Specifically, we describe the spike protein’s contributions, via its prion-like properties, to neuroinflammation and neurodegenerative diseases to clotting disorders within the vasculature to further disease risk due to suppressed prion protein regulation in the context of widely prevalent insulin resistance and to other health complications. We review both cellular pathologies and the expression of disease that could become more frequent in those who have undergone mRNA vaccination. We outline various pathways through which these proteins could be expected to distribute throughout the body. We propose that vaccine-induced spike protein synthesis can facilitate the accumulation of toxic prion-like fibrils in neurons. Based on in vitro and in vivo experimental evidence relating to prion and prion-like disease, we extrapolate from the compelling evidence that the spike glycoprotein of SARS-CoV-2 contains extended amino acid sequences characteristic of a prion-like protein to infer its potential to cause neurodegenerative disease. Human prion protein and prion-like protein misfolding are widely recognized as playing a causal role in many neurodegenerative diseases.
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