Exogenous AS a driver of disease? What does “denatured protein” mean?

[Little_apple]

Meat and eggs contain alpha synuclein.

I therefore asked my neuro if eating alpha synuclein, exogenous alpha synuclein, can contribute to the excess alpha synuclein created in PWP and be a driver of the disease.

He said, “no because it’s denatured.”

He has given me incorrect info before so I am questioning this. I’ve written to multiple doctors to ask this. No response. I just asked a nutritionist who specializes in medically used keto and she did not know.

Please, can you help me determine this?

[Bolt_Upright]

I found this:

de·na·ture

/dēˈnāCHər/

past tense: denatured; past participle: denatured

take away or alter the natural qualities of.

"this system denatures education"

make (alcohol) unfit for drinking by the addition of toxic or foul-tasting substances.

Biochemistry

destroy the characteristic properties of (a protein or other biological macromolecule) by heat, acidity, or other effects that disrupt its molecular conformation.

[Little_apple in reply to Bolt_Upright]

what I have read about denaturing , leads me to think it is similar to unfolding. So the protein is unfolded? Can it be re-folded and or misfolded as in misfolded AS? My lack of scientific understanding is obvious. Why I can’t get an answer to the exogenous AS question baffles me. I wrote to Dr. Datis Khazarian , author of “Why isn’t my brain working” and he does not know. No response from the many other doctors I’ve asked.

[Bolt_Upright in reply to Little_apple]

I don't think we can know anything. I think 50% of what is known is 100% wrong.

I found another definition for you:

What is denaturation in biology?

denaturation, in biology, process modifying the molecular structure of a protein. Denaturation involves the breaking of many of the weak linkages, or bonds (e.g., hydrogen bonds), within a protein molecule that are responsible for the highly ordered structure of the protein in its natural (native) state.

[WinnieThePoo in reply to Little_apple]

No. It's not similar. Protein folding and misfolding refers to the way in which the the newly synthesised protein molecule folds into its unique 3D structure, which determines its functionality.

Food is denatured by digestion. The proteins are not unfolded, but chopped into smaller amino acids. The digested amino acids are rebuilt in the body into new proteins, which then fold to their correct (or incorrect shape)

This video covers that digestion process

youtube.com/watch?v=a6vEIdO...(Not working as expected?)

[Little_apple in reply to WinnieThePoo]

“The digested amino acids are rebuilt in the body into new proteins, which then fold to their correct (or incorrect shape)”

Based on this statement, can the digested alpha synuclein be rebuilt in to “new” AS and therefore add to the volume of AS in the gut?

When amino acids are “built in to new proteins” is this based off of what the body needs or are they “built” in to a new form of what they were? AS in to AS?

It is my understanding that AS is an immune response and is therefore a response to the disease pathology which then contributes to it. Therefore, eliminating exogenous AS would of course not be a cure but could ingesting exogenous AS be contributing to disease pathology?

[park_bear in reply to Little_apple]

Amino acids are basic building blocks and can be used to create any protein by the body's protein assembly process. This occurs inside cells. Amino acids will not randomly reassemble into AS.

As to the effect of ingesting exogenous AS I have already provided you with the state of the current research below. I suggest you take a look at it since you keep asking the question.

[Little_apple in reply to park_bear]

The question remains bc the research is inconclusive and contradictory

[WinnieThePoo in reply to Little_apple]

First, alpha synuclein isn't digested and so can't be rebuilt into anything. The amino acids that a-syn is broken down into can build more than just a-syn. Think of it like a lego set. You break down your lego castle. You don't have to just build a castle from the bricks. You might, with some other bricks build a boat.2nd - you want a-syn. The last thing you want is to eliminate it. It is essential for neurons to function. It's the misfolded form you don't want

[Little_apple in reply to WinnieThePoo]

Excellent analogy. If it is just misfolding AS that is the PD problem and not the volume of AS, then wouldn’t interventions to remove AS be the wrong course of action? Ambroxol being one example.

A low protein diet shows a reduced risk and slower progression. Perhaps this is just correlational or maybe increased protein intake increases misfolding of proteins?

[WinnieThePoo in reply to Little_apple]

A lot of this stuff is complicated. It's fair to say , with regard to a-syn, that there is no definite consensus. The definitive diagnosis of PD has always been post-mortem evidence of Lewy body damage to neurons. Lewy bodies are the final stage of aggregation of a-syn misfolding , although they contain a lot of other stuff. Levels of mis-folded a-syn are significantly raised in people with PD - but it is not clear whether this is the cause of the disease or a response to it

There are significantly raised numbers of Paramedics at the scene of major car crashes, but that doesn't mean they caused them

Regarding mis-folding, most of the experimental drugs, including the Biogen BIIB054 monoclonal antibody - which was the drug trial I participated in, target the mis-folded form and not a-syn generally

[Little_apple in reply to WinnieThePoo]

I think Ambroxol is targeting AS in general, not just misfolded.

[WinnieThePoo in reply to Little_apple]

Ambroxol is a cough medicine. BIIB054 was a PD specific monoclonal antibody.

pubmed.ncbi.nlm.nih.gov/232...

[park_bear]

There is pretty good evidence indicating Parkinson's is primarily a result of toxic exposure. For example, see my writing here: tinyurl.com/k3vt26py

So I am skeptical of food as a source, but it is not impossible. Here is the current state of research:

nature.com/articles/s41531-...

Vertebrate food products as a potential source of prion-like α-synuclein

" Overall, research to date has yet to directly test the contribution of dietary α-synuclein to the mechanism of initiation and progression of the disease. However, numerous experimental findings, including the potent seeding and spreading behavior of α-synuclein fibrils, seem to support, at least in part, the feasibility of an infection with a prion α-synuclein particle via the GI tract. Further studies are required to determine whether dietary α-synuclein contributes to seeding pathology in the gut."

Speculative:

academic.oup.com/nutritionr...

The intestinal luminal sources of α-synuclein: a gastroenterologist perspective

" The present narrative review extends the current mucosal origin of Parkinson’s disease, presenting the possibility that the disease starts in the intestinal lumen. If substantiated, eliminating the nutritional sources of aSN (eg, applying a vegetarian diet) might revolutionize the currently used dopaminergic pharmacologic therapy."

mdpi.com/2073-4409/10/5/1111

Cross-Reactivity and Sequence Homology Between Alpha-Synuclein and Food Products

" It is hypothesized that luminal food peptides that share cross-reactive epitopes with human α-synuclein and have molecular similarity with brain antigens are involved in the synucleinopathy. The findings deserve further confirmation by extensive research."