Suggesting that Viral Infection Can Promote the Spread of Protein Aggregates in the Brain

There is an ongoing debate over whether or not persistent viral infection plays an important role in the development of Alzheimer's disease. That is largely focused on the function of the immune system, given the demonstrated relevance of chronic inflammation and microglial dysfunction to the progression of neurodegenerative conditions. Here, however, researchers provide in vitro evidence to support the hypothesis that viral infection can promote the spread of misfolded proteins between cells in the brain. Aggregates of misfolded or otherwise harmfully modified proteins such as amyloid-β, α-synuclein, and tau are involved in many neurodegenerative conditions. Exactly how these proteins spread as the condition progresses is an area of considerable interest in the research community.

Transmission of aggregates could involve direct cell-to-cell contact, the release of "naked" aggregates into extracellular space or packaging in vesicles, which are tiny bubbles surrounded by a lipid envelope that are secreted for communication between cells. "The precise mechanisms of transmission are unknown. However, it is an obvious guess, that aggregate exchange by both direct cell contact and via vesicles depends on ligand-receptor interactions. This is because in both scenarios, membranes need to make contact and fuse. This is facilitated when ligands are present that bind to receptors on the cell surface and then cause the two membranes to fuse."

Researchers investigated the intercellular transfer of either prions or aggregates of tau proteins, as they occur in similar form in prion diseases or Alzheimer's disease and other "tauopathies". Mimicking what happens as a result of viral infection, the researchers induced cells to produce viral proteins that mediate target cell binding and membrane fusion. Two proteins were chosen as prime examples: SARS-CoV-2 spike protein S, which stems from the virus causing COVID-19, and vesicular stomatitis virus glycoprotein VSV-G, which occurs in a pathogen that infects cattle and other animals. Moreover, cells expressed receptors for these viral proteins, namely the LDL receptor family, which act as docking ports for VSV-G, and human ACE2, the receptor for the spike protein.

"We could show that the viral proteins are incorporated both into the cellular membrane and into the extracellular vesicles. Their presence increased protein aggregate spreading between cells, both by direct cell contact or by extracellular vesicles. The viral ligands mediated an effective transfer of aggregates into recipient cells, where they induced new aggregates. The ligands act like keys that unlock the recipient cells and thus sneak in the dangerous cargo. Certainly, our cellular models do not replicate the many aspects of the brain with its very specialized cell types. However, independent of the tested cell type producing the pathologic aggregates, the presence of viral ligands clearly increased the spreading of misfolded proteins to other cells. All in all, our data suggests that viral ligand-receptor interactions can in principle affect transmission of pathologic proteins."

"The brains of patients suffering from neurodegenerative diseases sometimes contain certain viruses. They are suspected to cause inflammation or to have a toxic effect, thus accelerating neurodegeneration. However, viral proteins could also act differently: They could increase intercellular spreading of protein aggregates already ongoing in neurodegenerative diseases like Alzheimer's. Of course, this needs further studies with neurotropic viruses. Clearly, the impact of viral infections on neurodegenerative diseases deserves in-depth investigation."



So.... the SARS-CoV-2 spike protein S, which your cells will produce after COVID19 vaccination with one of the current mRNA drugs, will be 'incorporated both into the cellular membrane and into the extracellular vesicles.' and 'Their presence increases protein aggregate spreading between cells, both by direct cell contact or by extracellular vesicles.'
because 'The viral ligands mediate an effective transfer of aggregates into recipient cells, where they induce new aggregates. The ligands act like keys that unlock the recipient cells and thus sneak in the dangerous cargo.'?

WTF!? I really want to see this paper on pubpeer with a very long comment list.

Posted by: Jones at October 27th, 2021 8:55 AM

There was a similar study suggesting that some cases of Multiple Sclerosis and ALS can be instigated or at least aggravated by an initial infection.

Posted by: Cuberat at October 27th, 2021 9:00 AM

Good news! Prevent neurotoxic proteins from spreading by NOT fasting.
I'm not much of a roundworm but I can do that. ;p

Researchers shed new light on molecular mechanisms in brain diseases

'The Rutgers researchers studied roundworms whose stressed nerve cells can extrude neurotoxic proteins in large packets called exophers and how specific stresses affect this extrusion. They found that specific cellular signals are needed to form exophers and, unexpectedly, that fasting dramatically increases the production of exophers. They also identified three cellular pathways that increase production of exophers during fasting.'

Posted by: Jones at October 27th, 2021 9:49 AM

1) The spike protein produced by the mRNA vaccines is non-functional (it's alway in the "open" state, it can't open an close like the wild type one, so it can't enter other cells like the virus does).
2) After production in the ribosomes, it's broken into pieces by the cell and those pieces are then presented in the surface of the cell to estimulate an immune response. So most of the proteins presented aren't the complete protein.
3) The amount of mRNA in the vaccine is much less than the amount in a regular infection (and at least 10 % of people in the world are already infected).
4) If you are vaccinated and you get infected, you will have much less viruses in your body and for less time than if not vaccinated.

Posted by: Antonio at October 27th, 2021 12:20 PM

@Antonio Thanks.

Posted by: Jones at October 27th, 2021 12:28 PM

More good news! AD cured, again!

Four commonly used medications reverse Alzheimer's disease in mice

Date: October 27, 2021
Source: Institute for Research in Biomedicine (IRB Barcelona)
Summary: ... Researchers have managed to reverse the symptoms of Alzheimer's disease in mice by administering drugs currently used to treat hypertension and inflammation in humans

NSAIDs: dexketoprofen and etodolac
Anti-hypertensives: penbutolol and bendroflumethiazide

Posted by: Jones at October 28th, 2021 6:52 AM

AD and murine models is an oxymoron.

Posted by: Cuberat at October 28th, 2021 5:18 PM
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