Parkinson’s disease (PD) is characterized by the loss of nerve cells responsible for producing dopamine, which causes movement difficulties and other symptoms. An important aspect of PD is the accumulation of a protein called α-synuclein in the brain, which triggers inflammation and worsens cell degeneration.
This study used a PD model in mice to understand the role of certain immune cells, called Th17 cells, which increase with the presence of α-synuclein in the brain. The inflammation caused by these cells seems to contribute to symptoms and disease progression.
The researchers tested abatacept, a drug used for arthritis that modulates T cell response. They found that abatacept reduced Th17 cells in the brain, improved motor function, and protected dopamine-producing nerve cells in the mice. This suggests that abatacept could be a potential treatment to reduce inflammation and slow the progression of PD.
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Emanuelfrb
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People have experienced serious infections due to abatacept's suppression of the immune system; some of these infections have been fatal. People with COPD are likely to get lung infections more often than usual. Some people have had anaphylactic reactions to the drug. Abatacept may cause otherwise slow-growing cancers to proliferate and spread, due to suppression of the immune system.[5]
Very common adverse effects (occurring in more than 10% of people) include upper respiratory tract infections. Common adverse effects (occurring in between 1% and 10% of people) include lower respiratory tract infections, urinary tract infections, herpes infections, pneumonia, flu, cough, high blood pressure, stomach pain, diarrhea, nausea, vomiting, upset stomach, mouth sores, elevated transaminases, rashes, fatigue, weakness, local injection site reactions, and systemic injection reactions"
Interesting. I just came across a study in MS that used N-acetyglucosamine to lower TH-17 levels beyond what the potent immune-modulating drug Glatiramer acetate could do. I wonder if we should be giving GlcNAc a second look for PD?jneuroinflammation.biomedce...
"N-acetyglucosamine (GlcNAc) is a triple modulator of inflammation, myelination and neurodegeneration."
"Prior to GlcNAc therapy, high serum levels of the inflammatory cytokines IFNγ, IL-17 and IL-6 associated with reduced baseline levels of a marker of endogenous serum GlcNAc. Oral GlcNAc therapy was safe, raised serum levels and modulated N-glycan branching in lymphocytes. Glatiramer acetate reduces TH1, TH17 and B cell activity as well as sNfL, yet the addition of oral GlcNAc dose-dependently lowered serum IFNγ, IL-17, IL-6 and NfL."
Totally different molecules, although their acronyms make things confusing. GlyNac is a combination of two amino acids, glycine and n-acetyl-cysteine. They are both precursors to glutathione, so taking them together is thought to increase the production of this important antioxidant.
GLcNAc is N-acetyglucosamine, an acetylated version of glucosamine, a natural sugar that in another form (glucosamine sulfate) is used for joint health. It's also abbreviated as NAG, which seems more to the point. I don't know why studies prefer GLcNAc.
This is an interesting story, but suggest to me a slightly different direction, not so much this molecule itself but the idea in general. Here's what I mean:
This is interesting because there is a relatively new field now called "structural chemistry," and some of them are starting to use AI to try to map out the topology of proteins including all their folding angles, and if they can do that they might be able to map out the exact shapes of the proteins and also they're matching receptor shapes that fit the proteins as lock and key..
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So I am hoping that maybe the PD research community, those working in alpha synuclein, May try to switch over to their direction.
If they are able to then do that they might be further able to rebuild the shape of the protein that has been misfolded like synuclein in PD, and then maybe through CRISPR engineering properly shaped protein, to properly fit the receptor, or an immune cell or antibody that can either clamp the molecule and bring it back out of the cell or start breaking it down for its components, both as per normal bodily function.
I was interested to see if there were other solutions to reduce TH17 cells. I specifically looked up Ketones.
Here's what I found.
ketones, particularly β-hydroxybutyrate (BHB), have shown potential to reduce Th17 cell activity. This effect makes ketones a point of interest for treating inflammatory and autoimmune diseases where Th17 cells play a role.
Mechanisms Behind Ketones’ Effect on Th17 Cells
Inhibition of the NLRP3 Inflammasome
BHB, the primary ketone body produced during ketosis, is known to inhibit the NLRP3 inflammasome, a protein complex involved in inflammation. This inhibition indirectly reduces Th17 cell differentiation, as the NLRP3 inflammasome is linked to the promotion of Th17 responses.
Gene Expression Changes in T Cells
Ketones have been shown to affect the expression of genes that promote the differentiation and activity of Th17 cells. Specifically, ketones may reduce the expression of RORγt, a transcription factor crucial for Th17 cell development.
Reduction of Inflammatory Cytokines
Ketones can reduce levels of inflammatory cytokines like IL-17, IL-1β, and IL-6, which are associated with Th17 cell responses. Lower levels of these cytokines contribute to a decrease in Th17 activity and associated inflammation.
Studies and Findings
Studies on the ketogenic diet and exogenous ketones suggest a decrease in Th17 cells and their inflammatory cytokines. In animal models of autoimmune diseases like multiple sclerosis (in its model form, experimental autoimmune encephalomyelitis), a ketogenic diet has been observed to decrease the infiltration of Th17 cells into affected areas, such as the central nervous system, reducing inflammation and disease symptoms.
Practical Implications
Ketogenic Diet: By inducing ketosis, this diet could help reduce Th17-mediated inflammation, potentially benefiting those with autoimmune diseases.
Exogenous Ketones: Ketone supplements, particularly BHB salts or esters, might also influence Th17 cells, though their effects are less studied than dietary ketosis.
Abatacept seems to be one of those drugs that intentionally weakens immune system and have some risks because of that, also seems to be pretty limited in application among the doctors. Found this on its brand website, there's more extensive details therein: "Increased Risk of Infection with Concomitant Use with TNF Antagonists, Other Biologic RA/PsA Therapy, or JAK Inhibitors." It seems to interfere with the immune system, intending to relieve joint arthritis, but also thereby exposes people to a lot of serious infections. Maybe it's early on in it's potential for PD, right now it sounds like a very risky trade-off.
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