Here is a very robust article on PD neurodegeneration. Read this and you will be up-to-date on what we know about how Parkinson's occurs and what causes it to progress.
ncbi.nlm.nih.gov/pmc/articl...
Fair warning, it is a fairly technical article.
One of the things we need to spend more time focusing on (here on this forum) is strategies to quell microglia. The microglia activate for a number of reasons and if you cannot manage to quell them, don't expect to slow disease progression very much
Great find!
The document is also available from this site (and it has a PDF option too):
Blaylock, the author, has a website, and sells a monthly letter the "Blaylock Wellness Report"
(49,95 USD) where he states : "How brain diseases like Alzheimer’s and Parkinson’s can be prevented", that is through nutrition.
Any idea of what it is ?
PS - You can also buy from his site some remarkable books, such a "The Healing Powers of Vinegar" (USD 14)
Thank you so much for this article, Hopeful88.
The conclusion is positive :
"The future treatment of Parkinson’s, and more importantly, prevention, may depend on utilizing compounds that suppress neurodegenerative immunity, and more importantly, excitotoxicity. Because of the complexity of the immunoexcitotoxic process, a number of possibilities now exist in attaining this goal."
What is R. Blaylock alluding to when he say "a number of [existing] possibilities" ?
Does anyone here have a clue ?
Although I find all new evidence welcomed, I find PD pathogenesis away from a-Synuclein very distressing, in that I have bet the farm on that ! Since Dopamine replacement is doing absolutely nothing for me, my main treatment is based on Xanthohumol, and I based that on its mechanism of action being similar to Nilotinib. See a post here if you are interested on Xanthohumol :
healthunlocked.com/parkinso...
But feels like I am chasing my tail, HOW is one to know if an a-Synuclein targeting treatment is working ? HOW long should I persist till i give up ? Burning questions that I am afraid have no answer atm.
Just a heads up. The article is by Russell Blaylock, who I think is known for espousing unconventional medical theories. As the Wikipedia states, "Blaylock has endorsed views inconsistent with the scientific consensus..."
Let the reader beware.
Technical ? that leaves me out.
I have begun perusing Blaylock's 2017 PD paper and have been paying
attention to the citations. I'm up to "c. Inflammation, microglia, and
alpha‑synuclein". Yes, Blaylock is a maverick, but in his career, he
seems to integrate medical findings into reasoned, though often unwanted
hypotheses. As far as I've read thus far in his new PD paper, he's
building a well referenced rationale. That doesn't make it necessarily
valid, but the physiological findings which are his building blocks make
his model worthy of consideration.
At least one aspect of safinamide (Xadago®) is consistent with Blaylock's concerns regarding excitotoxicity:
"Safinamide is an oral, once a day adjunctive therapy for any stage of
Parkinson's disease (PD). It is a unique molecule with a novel dual
mechanism of action based on the enhancement of the dopaminergic
function (through potent reversible inhibition of MAO-B and of dopamine
uptake) and inhibition of the excessive release of glutamate."
Perhaps I have read too many science articles but this hypothesis is vague. What is missing is the cause of the excitotoxicity?
There are other articles which mention 'excitotoxic' substances in relationship to PD, specifically quinolinic acid:
Excitotoxicity of quinolinic acid: modulation by endogenous antagonists
ncbi.nlm.nih.gov/pubmed/167...
Quinilinic acid is one of the products of the kynurenine pathway.
The Involvement of Neuroinflammation and Kynurenine Pathway in Parkinson's Disease
hindawi.com/journals/pd/201...
Really, he should have been more specific with his hypothesis...and it is just that, a hypothesis.
There's a lot of very useful information presented in the paper, and it's summarized in a very easy to understand format.
Remember, Silvestrov, that most folks have no prior knowledge of what's presented in the paper. Heck, up until now, microglia was scarcely a topic that was ever mentioned on this forum.
Of course it's not possible for Blaylock to mention everything. I kept wondering when he was going to mention NF-κB since it's so important to microglia and immune response.
Most of what Blaylock is saying is correct.
Yes, he makes the hypothesis about excitotoxicity. It's no secret that cells affected by PD become pretty crippled over time, so it makes sense that they lose their ability to control intracellular concentrations of calcium and are very sensitive to glutamate. In such a harsh environment, these cells are not able to maintain themselves in situ. The jury's still out, but it does seem quite plausible that excitotoxicity plays a part.
All in all this is a pretty helpful piece. Why? Because from a high level, it outlines a way forward towards the neuroprotective actions we can take.
We can inhibit NADPH oxidase. We can quench hydroxyl radicals. We can protect cell membranes and mitochondria. We can quell microglia to some extent. We can also help make microglia less pathogenic. We can inhibit iNOS. We can try to reduce excess intracellular iron. We can increase the expression of heat shock proteins. We can try to boost production of trophic factors like BDNF, GDNF, and NGF. We can boost intracellular magnesium and reduce intracellular calcium. We can help restore the blood-brain barrier. We can try to keep the cholinergic system innervated with a healthy supply of acetylcholine. We can boost autophagy and mitophagy where they are impaired. We can boost mitochondrial potential. We can try to protect against DNA damage. And so on.
I know our ability to do these things isn't perfect. But most people don't understand, the more of these targets you address, the better you'll come out long term.
This is especially true for those who have bilateral symptoms of parkinsonism or those who show cognitive impairment early on. Most people don't realize that synucleopathies often end in dementia. We need to do a better job of explaining to people, in a way that isn't too hard to understand, the things they can do right now such that they'll have more quality years for the future.
Hi you really seem to know yr stuff! I’ve read most of yr posts which are so interesting. I just wonder what supplements you take. It’s all a bit overwhelming !! Thanks
Blaylock 2017 has provided a literature review supporting his model
wherein microglia and excitotoxins can induce neuronal death, eg, in the
substantia nigra.
ncbi.nlm.nih.gov/pubmed/244...
For instance, Blaylock writes in 2017:
"Ling et al. demonstrated that exposing animals prenatally to LPS
reduced the number of dopamine neurons in the substantia nigra, and that
exposing these animals later in life to subtoxic doses of rotenone led
to a significant loss of DA neurons.[145]"
Blaylock used the word hypothesis in a 2011 paper:
ncbi.nlm.nih.gov/pubmed/218...
His 2017 essay is an elaboration of his 2011 "hypothesis" (more thorough, with newer references included).
Testable hypotheses (perhaps one narrow focus at a time) can be derived from his 2017 literature review.
In one of his letters he mentions ibuprofen is an anti-inflammatory that is doing well for neurological brain diseases
Be careful with that. Ibuprofen isn't really something that you're supposed to take on a daily basis. Long term consumption of ibuprofen is linked with an increased risk of heart attack and it's also linked with stomach problems if you take it for too long.
Thank you, no I don't take any. It raises my blood pressure. I guess what I was trying to say is that it supports that inflammation Theory.
Let me know when the cliff notes come out.
Blaylock's 2017 review and model calls attention to quinolinic acid:
"With microglial activation, we see a simultaneous release of neurotoxic
levels of both proinflammatory cytokines and excitatory amino acids,
including glutamate, aspartate, and quinolinic acid [96,120]".
96. Guillemin GJ; Quinolenic acid, the inescapable neurotoxin.
He comes across as a salesman trying to convince me that this years model is better than the last when they're both the same. Although the specifics are slightly different, I think a lot of the article is repackaging known information in a way that makes him seem like an innovator.
Maybe I didn't read it thoroughly enough but I was not impressed.
Does regular driving have a positive impact on the PD?
Best Forms Of Magnesium I Have Ever Tried!
What if we are approaching this all wrong?
The best advice I can or may ever give to anyone who has Parkinson's especially the newly diagnosed .
Add Idebenone Back to my Stack?
