Is alpha synuclein aggregation an immune response?

My theory is that alpha synuclein aggregation is an immune response. If this is true, is attempts at removing the alpha synuclein aggregation akin to making the fire trucks leave the fire? Is the aggregation of alpha synuclein the bodies attempt to address or suppress the root cause?

I found this which I think supports this theory.

“Alpha-synuclein (αS) has many biophysical characteristics of antimicrobial peptides and binds small vesicles such as those carrying endocytosed viruses. It is induced in nerve cells in response to viral and bacterial infections. It renders the nerve cell resistant to viral infection and propagation.Oct 30, 2019”

ncbi.nlm.nih.gov/pmc/articl...

Convincing evidence supports the premise that reducing α-synuclein levels may be an effective therapy for Parkinson’s disease (PD); however, there has been lack of a clinically applicable α-synuclein reducing therapeutic strategy. This study was undertaken to develop a blood-brain barrier and plasma membrane-permeable α-synuclein knockdown peptide, Tat-βsyn-degron, that may have therapeutic potential. The peptide effectively reduced the level of α-synuclein via proteasomal degradation both in cell cultures and in animals. Tat-βsyn-degron

nature.com/articles/s42003-...

Gut-to-brain propagation of pathologic α-synuclein via the vagus nerve causes PD

cell.com/neuron/fulltext/S0...

If alpha synuclein is a response to the root causes of PD but not a root cause, than what are the root causes of PD? I believe the root causes are an interplay between genetics which increase risk, and broadly and simplistically speaking mitochondrial and glial cell dysfunction.

I intend on writing more later about astrocytes (a type of glial cell) and how Excitotoxicity leads to dopaminergic neurons being put in to a state similar to hibernation (zombie state). I believe this pushes them in to senescence.

I think Dr. Sackner Bernstein is partially correct. I appreciate his intellectual inquiry but I do not believe there is “too much dopamine” unless one is medicating with too much additional dopamine. I do not think there is “too much dopamine” but that the dopaminergic cells we are told are all dead, are not all dead as we are simplistically told. It’s a process. Some are in a zombie like hibernating state. Can they be revived or should they be cleared out to not be bad apples rotting the bunch? I think the latter is more likely which is where the importance of senolytics comes in.

Thank you for reading. I assume I have typos but am not proofreading due to time constraints.

One more link

Astrocytes: Role and Functions in Brain Pathologies

frontiersin.org/articles/10...

[Bolt_Upright]

Good job CC!

[park_bear]

Yes there is evidence that α-synuclein is an immune response. However, it is an immune response gone awry because it can be caused by certain chemicals, which are not pathogens.

[Hidden in reply to park_bear]

Yes, which makes it an over response like autoimmunity. Viruses contribute to ALZ. That is quite established. There is evidence of the same for PD.

[Hidden]

Viruses are known to cause neurological problems. Herpes is a common example. Is it the virus or the immune response to it? Should we pursue anti viral medication as a PD therapy?

About 60% of people are estimated to have the herpes virus

news-medical.net/amp/health...

Brain inflammation, signs and causes including herpes

youtu.be/oQCmjX33pLI(Not working as expected?)

[MarionP in reply to Hidden]

You can also get a similar panoply of symptoms from another virus that a majority of humans are believed to have in their brains: toxoplasmosis. What keeps it at Bay is a healthy immune system, and when the immune system loses certain aspects of function, the the mechanism is in that the viruses free to wreak its havoc. Different than an immune response wreaking havoc. Also, certain cancers are treated by reducing the immune response. The general idea is not a bad one. The problem again is having information established to try to answer it and what it will take to answer yeah, and further what will it take to design or develop a response. Most current treatments that modify the immune system to treat a particular disease have scads of side effects that cause their own disease problems.

[Hidden]

healthunlocked.com/cure-par...

[jeffreyn]

An alternative theory is that alpha synuclein production is an immune response. Aggregation occurs when there is too much alpha synuclein produced. [1]

[1] Alpha synuclein, the culprit in Parkinson disease, is required for normal immune function, Md Masud Alam et al., Cell Reports, Jan 11 2022.

pubmed.ncbi.nlm.nih.gov/350....

The opening sentence of the research paper states the following: "Alpha synuclein (aS) plays a key role in the pathogenesis of Parkinson disease (PD). The best evidence for this is that expression of multiple genes for aS results in severe inherited familial PD (Chartier-Harlin et al., 2004; Polymeropoulos et al., 1997; Singleton et al., 2003)."

I understand this to mean that too much alpha synuclein (e.g. by duplication/triplication of the SNCA gene), can, in itself, cause PD.

In the Discussion section of the research paper, they state the following: "... if these stimuli persist chronically, either due to repeated infection or a failure to effectively contain commensal bacteria, the stimulation of aS would be unremitting."

I understand this to mean that chronically-persistent stimuli could result in too much alpha synuclein.

So, it seems to me that all that might be required is a way to prevent too much alpha synuclein being produced (e.g. Annovis Bio's approach, using Buntanetap/Posiphen). We might find out quite soon, as Buntanetap is about to enter Phase 3 trials.

healthunlocked.com/cure-par...

[kevowpd in reply to jeffreyn]

I suspect that a condition that has evaded mankind's efforts to effectively treat long term is probably quite complex. Not that complex that it never manifests, but complex enough that we can't yet figure it out and that it occurs in a small percentage of people.

mdpi.com/2218-273X/12/2/228...

[jeffreyn in reply to kevowpd]

Hay, I'm the PwP, not the research scientist. I'm entitled to some semantic sloppiness!

🙂

[kevowpd in reply to jeffreyn]

Of course. I linked the article bc I thought you particularly would find it interesting.

[jeffreyn in reply to kevowpd]

Absolutely! Thanks.

[Hidden in reply to jeffreyn]

“that chronically-persistent stimuli could result in too much alpha synuclein.” Exactly. So we are extra susceptible to this “stimuli.”

Thank you for the thought provoking response and links!

[Despe]

Good job, CC.

I have repeatedly commented that neurons don't die, they hibernate.

youtube.com/watch?v=1_DBnv3...(Not working as expected?)

[Hidden in reply to Despe]

Despe, it was you my friend who introduced me to this revelation and it was pivotal for me!! Now I want to understand how and why and what can we do! Senolytics? Increased oxygen? Reduce toxin exposure? Increase blood flow? Increase BDNF? Reduce cortisol? Nicotine? Reduce inflammation? 😊

[Despe in reply to Hidden]

Hi, CC!

All of the above, I imagine, although I am not a doctor/scientist.

[Despe]

youtube.com/watch?v=TIZ-cIb...(Not working as expected?)

[Despe]

I checked his fees: One hour session is $1,000!! Thirty minutes $500. Unbelievably expensive.

[Hidden in reply to Despe]

Who?

[Despe in reply to Hidden]

Dr. John Bergman, the one on the videos above.

[Hidden in reply to Despe]

Oh! $1,500 for my appointment with Dr. Todd LePine.

[MarionP in reply to Hidden]

tried to tell you life is expensive if you really want the miracle goods. Gee and think about that, that's all from a guy who does not have a cure, just a good story. For treatment, what's that going to cost?

"Oh for that we have to move to a different price menu. Much much higher. See the menu we're working from today is the introductory "there's one born every minute" menu. If we're talking actual treatment, we have the premium quality, more Michelin stars menu, called the "never give a sucker an even break" price menu."

[Despe in reply to Hidden]

WOW!