TWiN 30: Gut to brain spread of alpha-synuclein in Parkinson's disease

[@westfield90]

This and Alzheimer’s are such tragic cruel diseases. I pray we get a breakthrough treatment or cure in our lifetimes. Too many families are suffering watching their loved ones deteriorate

[@notbuyingit2204]

Do some research on a possible connection between parasites and Parkinson's disease (also MS, Lou Gehrig's disease, etc. etc.) It's a deep rabbit hole.

[@nycpaulll]

This 82 yr old English major, PR career, science nerd eagerly awaits each video for bits and pieces of amazing science you and your guests present. I so appreciate the periodic backup for a definition of a terms that lets me hold on to the exciting flow of research information you share. Thank you all.

[@elinannestad5320]

fascinating. My first outing from weekly watching TWiV. I really appreciate the effort to explain things to all of us.

[@Polkadotpup]

Omg, this group of individuals are brilliant. I’m guessing they were born this way. Amazing. I just listened in awe and was thankful someone understands this. They are so young and you can see their focus.

[@markh3387]

There is a human study back in 2013 evidencing alpha synuclein (aS) in upper and lower gut of a wide set of patients up to 8 years before they developed Parkinsons PD. Theres another study evidencing 3 patients with Pure Autonomic Failure PAF (without brain MRI involvement) many years before 2 of them developed Multi System Atrophy MSA, and the third PD. A 2020 mouse study has created PAF without motor issues, showing aS travels bilaterally from celiac ganglion to gut and spinal cord, up to CNS. A 2019 study shows vagus nerve atrophy in living MSA and PD patients, but not stroke or other forms of parkinsonism. There appears no doubt of a gut brain connection in MSA and PD, and interestingly aS tends to climb upwards to CNS, caudal rostral. There is a new SOC MODEL, hypothesising a 'brain first' and 'body first' parkinsonism... as both forms are now proven in various cases. It is curious why synucleinopathies are not centralised by Immunologists, as aS is a substrate of Transglutaminase 2, and both are part of our adaptive/innate immune. Great to see this is now gathering pace as 'time is brain' in these patients. Hope this is helpful.

[@barbmullen9923]

Thanks for this!

[@spocksdaughter9641]

Appreciated!

[@liliaflores6056]

Thank you for the information 🙏

[@zinnialady5153]

Enjoyed this. Also appreciate Tim defining things. Helps me to understand a bit better.

[@richardalcorn7187]

Fascinating discussion

[@daisyy99]

My late husband had Parkinsons for years. I noticed when he ate too much meat his system was slow and when he ate only vegetables he was was improved.

[@kelpszoidzlzelps2566]

My sister was a strict vegetarian as I was, for most of life--over 50 years. My sister was a big green leafy veggies fan --then PD struck her about 7 years ago. Now, due to the gut to brain lectin connection, experimenting in carnivore diet past 6 months. Time will tell. For me, switching to meat was a magical cure for obesity and high blood sugar. For my sister, the rat studies observing plant lectins climbing up the vagus nerve into the brain is a wake up call.

[@purelifedirtywater]

No one ever mentions the cause of Parkinson's. Pesticides and herbicides, which are neurotoxins to insects, have the same effect on the human nervous system if exposed over long periods of time. A lot of farmers in California and Germany are getting diagnosed with Parkinson's. I guess profits are more important than human lives nowadays.

[@salvadorhirth1641]

One key for ellucidating a number of neuronal diseases, among other diseases, is why inclusions ( of proteins that are not supposed to be in the nucleus of cells ) do occur. Could ribosomal slippage create import signals in peptides, I believe it's something that deserves scrutiny.

[@ianlondon2888]

People with Parkinsons can also die of cardiac arrest, complications of falls. Pneumonia is a preventable cause of mortality; the cause is generally aspiration. If the person with Parkinson's has a care taker, aspiration risk should be very minimal.

[@liliaflores6056]

Thank you 🙏

[@JW4REnvironment]

Interesting that Parkinson’s may get started in the gut. My grandmother showed the early sign of constipation that was discussed by Tim well before her unfortunate diagnosis of Parkinson’s….Did Braak publish his pivotal work on the anatomy of Parkinson’s in about 2003?

[@cyberbob4111]

Tim did a very good job, thank you!

[@lindascanlan6317]

I remember always having "stomach" issues as a child and young adult to this day...not at all surprised at the gut/brain relationship....

[@markh3387]

Look up NodThera, it has created an NLRP3 inhibiting drug that it is currently trialling in PD. NLRP3 is linked to aS upregulation, mouse studies show inhibiting NLRP3 reduces aS aggregation. NLRP3 is also upregulated in AD

[@elkabong6429]

My paternal grandmother had Parkinson’s, my aunt (father’s sister) had it and now, tragically, my step-mom has it. So, almost all of the women in my father’s life have had Parkinson’s disease. He’s now a caregiver at the age of 95. My stepmom is only 78. Wasn’t supposed to be this way.

[@luisfernando-mm3jt]

Thanks for sharing

[@peterjf7723]

Alzheimer's is a horrible disease, an aunt of my wife's died from it. Also my university chemistry professor developed Alzheimer's after he retired. I was friends with his children so had kept in touch. He was aware that his brain was failing, he would be talking about something and lose track of what he was talking about. When I last saw him it was hard to know if he was talking about real events or if it was confabulation.

[@notbuyingit2204]

Research the possible connection between Parkinson's disease and parasites -- Alzheimer's has similarities to Parkinsons. Use only independent sources, nothing from mainstream (like this video).

[@andresdelapenaavila9704]

Miss you guys, but finally 🤩

[@lindascanlan6317]

It's all so fascinating....but how does this brain/gut theory impact trauma and the effects of profound trauma and PD.

[@sarahxmate]

There are horse flies all over the mountains in Switzerland

[@mimiing7145]

51:00 "the reviewers DID NOTHING" HAHAHAH i felt that

[@malovela]

I wish I understood any of this.

[@amreshyadav2758]

how could this protein transpoted in nueron, thats in vegus nerve?

[@markh3387]

Hi Found some really interesting studies in protein misfolding in myopathy (desmin), and Chronic Kidney Disease (CKD). Underlying mechanism appears to be oxidative stress caused by Trimethylamine (TMA) made by gut bacteria, converted to Trimethylanine N-Oxide (TMAO) by FM03 in the liver. High circulating TMAO found in CKD, PD & MSA, associated to disease severity! Loss of Hydrogen (H2) in endoplasmic reticulum seems to have inverse relationship with TG2. TG2 upregulated in CKD, PD, MSA (and many other neurodegenerative diseases). Si based H2 treatment is reversing CKD, PD & AD in murine studies. THIS DEMONSTRATES PROTEIN MISFOLDING OCCURS THROUGHOUT THE BODY, CAUSED BY ENDOPLASMIC RETICULUM STRESS. Hope this helps

[@liliaflores6056]

Thank you for the information 🙏

[@susanedghill6597]

You are obviously not trying to explain to the older generation.

[@markh3387]

Hi, 2023 has been a watershed moment in highlighting how aS is upregulated by NLRP3 inflammasome, leading to aggregation. A company called NodThera has just reported the first ever NLRP3 inhibitor used in clinical studies, using aged patients. Several 2023 studies now shows how curcumin reduces NLRP3 and aS in 3 different types of mouse models of PD. Interestingly, a Mar23 autopsy study for the first time found aS in the bladder of MSA patients, showing that it is not isolated in the brain. This study went in to show how aS spreads from bladder to spine nerves that lead to brainstem. Whats really interesting about this study is that it also found aS in control patients who had UTI infections but did not display Parkinsonism before time of death... highlighting that aS upregulates in UTI, but is cleared out of the body in patients with healthy immune. Low IL10/high NLRP3 if found in UTI infections in various studies. In short, aS is part of our normal immune but seems to become pathogenic in the presence of high circulating NLRP3. NLRP3 increases as we age. Hope this helps explain things a little clearer in the context of age.

[@markh3387]

Sorry, should have highlighted that the 'glymphatic system' has been found to be faulty in neurodegenerative patients

[@lindascanlan6317]

Does starving the body of glucose impact the production of alpha synuclein? I'm on keto..have PD and feel strongly there may be a positive impact because I feel better...also as an aside - Vince - I also have Epstein Barr Virus and my titers are going down...I've been scrupulously following keto since Feb 1, 2022...

[@lindascanlan6317]

Does the mechanism of autophagy clean out these harmful proteins?

[@jdr9419]

I had a cousin who had Parkinson’s as a young woman. Unfortunately, she has succumb to the disease.

[@larryplating8036]

WOULD YOU ADVOCATE TO ADD RADON IN THE WATER? Why would you advocate for a neurotoxin like Hydrogen Fluoride be put in municipal water supplies. HF concentrations in the aquifers continues to increase.

[@larryplating8036]

Do you think it is possible that the proliferation of hydrogen hexafluoride in the municipal water supply could be a contributing factor to increase Parkinson’s. Hydrogen hexafluoride is a neurotoxin.

[@holgol00]

Sound?

[@PifflePrattle]

Hearing aids?

[@holgol00]

@@PifflePrattle maybe

[@holgol00]

@@PifflePrattle sound came back.

[@taracat7141]

Too many grey areas in this video's research....