ON THE STAGE 4 CANCER AUTOBAHN: THE GRP78 BRIDGE BETWEEN THE TUMOR MICROENVIRONMENT AND NEURODEGENERATION
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February 10, 2022

One little-discussed, but, in my opinion, extremely important interaction of the Spike Protein is with GRP78. GRP78 can form a complex with SARS-2-S and ACE2 on the surface and at the perinuclear region typical of the endoplasmic reticulum in VeroE6-ACE2 cells and that the substrate-binding domain of GRP78 is critical for this interaction.


What does this mean?


Endoplasmic-reticulum-associated protein degradation (ERAD) machinery in combination with the ubiquitin-proteosome system (UPS) is thought to be the mechanism for quality control in long-lived cells such as neurons; hence, GRP78 is likely a critical component of the endogenous neuroprotective program.


The Spike BINDS to this, de facto impeding its functionality.  GRP78 plays a role in autophagic protein quality control, participating in the destruction of misfolded proteins in the cytosol. Therefore we can now observe a causal link to the appearance of neurodegenerative conditions.


Regarding cancer, GRP78 is involved in several aspects of cancer development including tumor survival and proliferation, chemoresistance, angiogenesis, and metastasis. Many tumor cells overexpress GRP78 on the outer plasma membrane. GRP78 can then be released into the bloodstream.


Indeed, high levels of GRP78 are present in those with COVID.


GRP78 is also instrumental in tumorigenesis. A referenced study suggested that GRP78va has the potential to influence survival of cancer cells in adaptation to ER stress through modulating UPR signaling.


Stop. It. Now. Especially before the very young are potentially affected.


Referenced/Related Papers


GRP78 at the Centre of the Stage in Cancer and Neuroprotection

https://www.frontiersin.org/articles/10.3389/fnins.2017.00177/full


High GRP78 levels in Covid-19 infection: A case-control study

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7674149/


The chaperone GRP78 is a host auxiliary factor for SARS-CoV-2 and GRP78 depleting antibody blocks viral entry and infection

https://www.jbc.org/article/S0021-9258(21)00552-4/fulltext