Things hidden inside misfolded proteins

"Anti-matter" in some ways

In memory of a dear friend who was gone too soon, and yes because of mRNA vaccine (clots)

I will try my best to make this understandable for most people, but there will be highly complex interactions cited, and you will benefit from knowing or reading previous articles published in this Substack.

For the most part, I try very hard to remain “professional” and not espouse opinions, especially ones critical of others, but this subject in particular and this article will be different. First, let us go back in time, this background is necessary to understand my position and opinions on many, many subjects in relation to SARS-CoV-2.

It is mid-2021, COVID is all the rage and the only talk in town, adding the allure of social media “clout” and (mis)guided by certain research topics and the incapacity to do proper research, certain individuals that would later become “Covid influencers” start pushing one specific narrative.

The world was doomed, we would all die of prions and amyloidogenic diseases.

Within months, the amount of psychological damage I observed, done by said individuals was tremendous, to say the least, within weeks I found myself spending 20-hour days fueled by Modafinil scouring untold amounts of research to “prove” the “influencers” pushing this specific narrative were wrong while trying very hard to avoid mentally fragile people from committing suicide. I personally talked out dozens of people from taking the easy way out. It took a heavy burden on me. All that to no avail, people want to be sold narratives, the more dramatic the merrier. So I took the hard instance of blocking any single person covering the topics of amyloid or prions disease if they got any part of the pathway wrong. I can’t help thousands of people directly.

This “instantly block” decision became broader as narrative warfare increased and everything devolved into tribalistic narrative warfare. Since December 2019 I have been interested in only two things.

Finding the truth, and solving the puzzle.

It is okay to be wrong, I probably got things wrong multiple times, what I won’t stand for is grift and intellectual laziness. This hard instance based on my personal values, morals, and ethics led me to contribute, research, and develop a friendship with the person I sometimes refer to at the start of certain articles, crediting the person with important breakthroughs. Among the most gifted minds, I had the pleasure of interacting in my life.

In the process of researching the complexity of SARS-CoV-2 and its interactions, we always found ourselves at the fringe (as in at the edge) of scientific research, often going against the current dogmas of multiple fields. The first dogma we found ourselves in this position was the misfolded protein one, and incidentally among the most complex. With this background in mind, we now can cover the central theme of this article.

This drawing has nothing to do with the subject, I just like it.

If superantigens are the holy grail of vaccine research, misfolded proteins are the holy grail of protein research and most likely of biology itself. Uncovering how proteins fold and especially how they “mis”fold thus leading you to completely understand how they function, and so leading to “absolute control”. Certain small groups of very competent researchers from different fields all argued and argue to this day that the mRNA “experiment” was merely to gather untold amounts of data on this subject.

What are prion and amyloid proteins ?

For decades amyloids, and to a greater extent prions got a bad reputation as if they possessed quasi-mystical properties. They suddenly appear and accumulate and you get the short end of the stick. Biology is significantly more complex than that, and human biology is the most complex of all.

Both proteins have physiological, “healthy” roles. The precursor for amyloid beta (the one with the bad rep) plays a role in synaptic transmission and plasticity, for memory and learning too. Under normal function, amyloid plays an essential role in plasticity, memory, and cognitive function. Let us not forget that the same protein is also an antimicrobial, playing a role in protecting us from invading pathogens. In short, the protein is essential for brain function, but also as a “bug killer”.

The same for the precursor of the infamous “prion protein” (in literature it is called Scrapie Prion Protein - PrP Sc), specific sections of the protein have rather potent antimicrobial effects by breaking the membrane of other cells, very similar to LL-37 (a peptide I wrote about it last year). The normal prion (PrP C) has various physiological functions, such as maintaining the myelin (the insulation of your nerve fibers in a crude way) and regulating cell differentiation, cell death, and immune function, among other functions.

Even more remarkable, is that Prion Proteins can interact and bind to Amyloid Beta proteins, and the Prion Protein may have a role in regulating Amyloid Beta production and accumulation, in the presence of PrP Sc (the bad prion) there is an abundance and accumulation of the “bad amyloid”. And going further the authors propose and cite evidence on how PrP is a way for the body to deal with abnormal RNA, entraping them. The following section will be extremely important later in this article.

For example, Wang et al. [106] found that A oligomers, but not monomers, robustly
inhibited the reverse transcription activity of vertebrate telomerase enzyme TERT, probably by binding to the substrate RNA/DNA hybrid [106], raising the prospect that AB nucleic acid binding might also inhibit the proliferation of retroviruses

RNA/DNA hybrids are essential for retroviruses existential cycle.

If bacteria and fungi create biofilms to protect themselves and evade our immune system, some of these “bad” proteins are the human equivalent of a pathogen biofilm, but here to trap and kill them. Personal note, perhaps these “misfolded” proteins are a way for the body to tackle dealing with “unnatural substances” later.

Given the extensive role of Sepsis and Endotoxin in SARS-CoV-2, and especially mRNA-induced dysfunction, we need to understand the role of these proteins in these conditions. Remarkably enough, it has been proposed that Prion Proteins directly modulate the immune response against LPS (Endotoxin) and have protective and anti-inflammatory effects. It also directly protects cells in your brain from inflammatory injury from TNF-Alpha, if you scour “prion/amyloid" diseases literature you will find the trend that TNF is one of the biggest contributors to the accumulation of these proteins.

Here is an extensive paper on how Amyloid-β Peptides protect, its antimicrobial activity, and can entrap Candida. Also an RNA trap. One of the hallmarks of sepsis is the multi-microbial presence, meaning when sepsis advances enough, the body finds itself facing multiple pathogens at a systemic level (all over the body), no surprise sepsis accelerates amyloid plaques build up, and also directly affects the gut microbiome in a not so dissimilar way as SARS-CoV-2.

The 3 proposed hypotheses on how systemic inflammation drives neurodegeneration. Given how SARS-CoV-2 and its Spike Protein interact with both fungal and bacterial biofilms and can modulate the toxins produced by bacteria, and biofilms produced by fungi, it shouldn’t be a surprise it shares, quite literally, every single pathway described below.

In a very recent paper, by using a fairly advanced and well-designed model for sepsis, authors come in agreement with recent propositions, that sepsis itself doesn’t lead to amyloid formation, but rather it accelerates what is already there. Of course, the immune system and inflammation itself are among the most complex aspects of biology, so it is somewhat of a “chicken or the egg” situation. But what could be so noxious to the body that it always “entraps” and deposits these proteins around the body ?

Now that we have a good idea of the hidden aspects of these poorly understood proteins, we can try to find a causal relationship with previous topics. Different types of Herpes viruses are found in prion diseases. My previous (and almost paramount reading if you want to truly understand this) article on HERVs has more information on the complex relationship between latent viruses and neurodegeneration.

The forgotten ghosts - HERVs

We are getting to the core of the issue, quite literally. I often expect at least some readers to click in the reference and read parts of the scientific papers, but in case you missed, one of the SARS-CoV-2 papers related to HERVs, there are a few lines of especially important information. Some of the microclots found in Long Covid have HERVs inside them.

Reactivated endogenous retroviruses promote protein aggregate spreading

Prion-like spreading of protein misfolding is a characteristic of neurodegenerative diseases, but the exact mechanisms of intercellular protein aggregate dissemination remain unresolved. Evidence accumulates that endogenous retroviruses, remnants of viral germline infections that are normally epigenetically silenced, become upregulated in neurodegenerative diseases such as amyotrophic lateral sclerosis and tauopathies. Here we uncover that activation of endogenous retroviruses affects prion-like spreading of proteopathic seeds. We show that upregulation of endogenous retroviruses drastically increases the dissemination of protein aggregates between cells in culture, a process that can be inhibited by targeting the viral envelope protein or viral protein processing. Human endogenous retrovirus envelopes of four different clades also elevate intercellular spreading of proteopathic seeds, including pathological Tau. Our data support a role of endogenous retroviruses in protein misfolding diseases and suggest that antiviral drugs could represent promising candidates for inhibiting protein aggregate spreading.

The involvement of ERVs in Prion diseases has been proposed for over a decade, not only by their immuno-stimulatory effects but the correlation by the higher presence of some of them in the nervous system, and even in the cerebrospinal fluids of patients with sporadic Creutzfeldt–Jakob disease (the super aggressive and fast one). There was a sufficient amount of evidence for this hypothesis so far, but here we have mechanistic evidence.

Reactivated HERVs can act as seeds for the continuous misfolding of proteins, in the presence of certain parts of these retroviruses, certain proteins continuously “misfold”. Perhaps primarily a forgotten or poorly understood defense mechanism, all these proteins and pathogens often share similar receptors, thus able to induce negative feedback loops.

Source

This is why I am so adamant about proper diagnosis, study, and long-term tracking and recording of not only infections but also latent pathogens. The long-term consequences of Sepsis are not only poorly understood, but not given enough attention, the same goes for “minor herpes reactivation”, with only fungal/yeast infections getting the attention they deserve.

Each of these contributes to a vicious, long-term cycle of disease, T-cell exhaustion itself is correlated with more amyloid accumulation in Alzheimer’s, and all described here can contribute to that via both directly inflammatory insult, and of course, HERV interactions. And this gives us a few problems.

These proteins, even “misfolded” are a paradoxical protective response, their build-up is correlated with the “slow burn” of brain function, but unlike what many spout (especially the ones I blocked), your body can deal with and clean misfolded proteins. And that is literally the problem, as the friend referred to at the start of this article once said “Too much of anything is bad for you”.

Enhanced Degradation of Misfolded Proteins Promotes Tumorigenesis

Highlights

• Tumor cells possess enhanced capacity to degrade misfolded proteins

• This higher capacity promotes antioxidant defense and tumorigenesis

• TRIM proteins promote proteasomal degradation of misfolded proteins

• Nrf2 mediates upregulation of both TRIMs and the proteasome in tumor cells

Excessive, speedy degradation of misfolded proteins promotes the creation and growth of cancer. And together with all this information we have a plausible “turbo cancer” hypothesis. For years observational studies have seen an inverse correlation between Cancer and Alzheimer’s, if you get one, you are “protected” from the other.

…between the risk of developing of cancer and AD, an inverse correlation is noticed: Patients with AD show 61% decreased risk of cancer incident compared to reference subjects. A negative association can suggest the possibility that susceptibility to one disease may protect against the other.

Source

When I and my friend were looking into this subject, we found a person who observed a trial for a misfolded-protein clearing compound, which was really successful, except for the annoying byproduct that almost all patients died from aggressive fungal infections following the clearance. It is what sent me down all these avenues.

This article was aimed at going out of the beaten path, there are many other aspects of misfolded proteins that I covered in the last 2 years that also play roles here, this is mostly aimed at the rather “hidden” roles of these proteins.

Hopefully, it helps people understand the complexity of our current and future situation better, this is by no means an attempt at being reductive. I plan on writing about how the body deals with misfolded proteins soon, as a follow-up, and how these things intersect.

I am grateful for both the continued support and the patience of supporters.

My AI-generated mage is absolute fire haha