Parkinson's Involves Autoimmune Response to Alpha-synuclein

[Wishful]

https://newatlas.com/medical/blood-analysis-signs-parkinsons-10-years/

I earlier posted speculation that a-syn is a possible factor in ME. Removal during sleep involves astrocytes, which might be malfunctioning due to ME. This latest report shows that a-syn binding to brain cells might make them targets for t-cells. The type of t-cell response changes over time (~ 10 years) from a strong response to an inhibiting response, then maybe no response.

I don't know whether this applies to ME, but it sounds like something that could be involved. Maybe we have higher levels of one form of a-syn (they vary in size and maybe binding sites) and our t-cells might respond differently to them, affecting brain function. Maybe a-syn binds to glial cells too, targetting them in an autoimmune response, messing up brain function.

A quick check turned up this paper: https://www.nature.com/articles/d41586-019-01832-0

It shows that interferon-gamma (which can be produced by t-cells, NK cells, and a few others) inhibits neural stem cells. Does anyone here know offhand whether a reduction in neural stem cells proliferation might cause some of ME's symptoms, such as brainfog?

 

[pattismith]

It's interesting to notice that synucleinopathies (Parkinson Disease, Dementia with Lewis Body and Multi System Atrophy) involve alpha synuclein protein aggregates in
-neurons
-small nerve fibers
-glial cells (brain and spinal cords)

SFN is common in these diseases, and often showing up before brain symptoms.

This means that some serious diseases can affect both Brain + Small nerve fibers.

@Pyrrhus , you assume a common pathogenesis in small fibers and brain of ME patients. I understood your hypothesis is common infection in the brain and small fiber cells, am I right?

 

[Pyrrhus]

Does anyone here know offhand whether a reduction in neural stem cells proliferation might cause some of ME's symptoms, such as brainfog?

I don't think anyone can answer that with any certainty. But there is a fascinating hypothesis that the symptom of depression is correlated with, and possibly caused by, a lack of neurogenesis in the hippocampus. Therefore, a reduction in neural stem cell proliferation may lead to the symptom of depression.
(Note that I am only referring to the symptom of depression, I am not referring to the diagnosis of depression, or any other definition of depression.)

@Pyrrhus , you assume a common pathogenesis in small fibers and brain of ME patients. I understood your hypothesis is common infection in the brain and small fiber cells, am I right?

I highly suspect a common pathogenesis in peripheral nerves and the brain of myself. I can't generalize the experiments I have conducted on myself to other people without conducting an appropriate clinical trial.

In my case, the evidence points to a persistent infection with Enterovirus A71. If you'd like to learn more about this, I am attaching the slides from a small talk I gave at Berkeley a few years back. (For privacy reasons, I have removed my name from the slides.)

Hope this helps.

 

[pattismith]

impaired autophagy seems also involved in Parkinson and Schizophrenia and Lewis Body disease, possibly via the mTOR pathway, and mTOR inhibitor promotes autophagy.

"Over the last decade, multiple studies have unveiled the complex role played by mTOR signaling pathway in cellular metabolism. Mao and Zhang discuss recent findings on the role of mTOR signaling pathway in metabolic tissues and organs including liver, adipose tissue, muscle and pancreas [21]. Sangüesa et al. highlight the consequences of mTOR activation by excessive consumption of sugar [22]. In addition to cellular metabolism, mTOR regulates autophagy. Wang et al. show that mTOR participates in dopamine receptor D3-mediated autophagy regulation [23]. Finally, Kim et al. found mTOR pathway activation by fluid shear stress and melatonin in preosteoblast cells [24]. "

IJMS | Free Full-Text | mTOR in Human Diseases | HTML (mdpi.com)

 

[pattismith]

I just realized that lipoic acid is an mTOR activator, so it's not an appropriate supplement if one wants to activate autophagy...

Alpha‐lipoic acid inhibits lung cancer growth via mTOR‐mediated autophagy inhibition - Peng - 2020 - FEBS Open Bio - Wiley Online Library

α-Lipoic Acid Interaction with Dopamine D2 Receptor-Dependent Activation of the Akt/GSK-3β Signaling Pathway Induced by Antipsychotics: Potential Relevance for the Treatment of Schizophrenia | Request PDF (researchgate.net)

 

[pattismith]

other autoantibodies found:

Angiotensin type-1 receptor and ACE2 autoantibodies in Parkinson´s disease​

2022

Therapeutical strategies blocking the production, or the effects of these autoantibodies may be useful for PD treatment, and the results further support repurposing AT1 blockers (ARBs) as treatment against PD progression.

https://pubmed.ncbi.nlm.nih.gov/35701430/