A Wise Person Told Me to Not Forget About... - Cure Parkinson's

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A Wise Person Told Me to Not Forget About TUDCA

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Bile Acid Signaling in Neurodegenerative and Neurological Disorders 2020 mdpi-res.com/d_attachment/i...

"4.2. Parkinson’s Disease

After AD, Parkinson’s disease (PD) is the second most common neurodegenerative disease marked by progressive motor deterioration. Dopaminergic neuronal death and α-synuclein-containing Lewy bodies in the substantia nigra are two known characteristics although the majority of PD cases are of sporadic origin [83]. Animal models replicate this pathology using neurotoxins, genetic mutations or combinations of the two [ 84 ]. Phenotypically, clinical diagnosis of PD is more recognizable at later stages, when motor deficits are apparent due to the misfolded α-synuclein proteins spreading to additional parts of the brain and subsequently affecting the substantia nigra. However therapeutic options starting prior to the onset of motor symptoms (prodromal phase), would be the most beneficial

in slowing the disease progression thus highlighting the importance of identifying key biomarkers for successful diagnosis [85].

PD research utilizing surgical rodent models of PD observed bile acid metabolism alterations and potential bile acid markers. Using a prodromal PD mouse model created by injecting human α-synuclein fibrils and human α-synuclein monomers (as a control) via stereotactic unilateral injection, serum and brain tissue from the mice was analyzed for metabolomics. Metabolite pathway analysis in the brain tissue of the α-synuclein fibrils treated mice yielded significant alterations of four biochemical pathways: taurine and hypotaurine metabolism, bile acid biosynthesis, glycine, serine and threonine metabolism and the citric acid cycle. The taurine and hypotaurine metabolism pathway that was disrupted includes taurine which has the crucial role in the conjugation of neuroprotective TUDCA and UDCA [ 86 ]. An adeno-associated virus-α-synuclein injected bilaterally into the substantia nigra

of rats noted that overexpression of α-synuclein, which additionally is expressed in enteric neurons, altered their gut microbiome. Along with diversifying the gut microbiome, this overexpression significantly increased the level of free bile acids and primary bile acids (CA, total MCA and β-MCA), and additionally increased secondary bile acids (taurodeoxycholic acid, taurohyodeoxycholic acid and

DCA) irrespective of influence from exercise [ 87]. Another study further clarified the presence of bile acids using a surgical mouse prodromal PD model, with three being found significantly decreased in the serum of the α-synuclein-fibrils-treated group: omega-muricholic acid, TUDCA and UDCA.

UDCA and TUDCA, both neuroprotective secondary bile acids that can pass the BBB, were markedly affected with a 17- and 14-fold decrease from the control group [ 88 ]. These surgical rodent model studies, replicating aspects of PD, shows increased research in this field will assist in therapeutic changes.

Other recent PD research has used anti-inflammatory secondary bile acids TUDCA and UDCA in experimental therapy studies. Decreased mitochondrial activity has been implicated in PD; the mitochondrial inhibitor 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) replicating glial activation and the pro-inflammatory cytokine cascade of PD. A series of TUDCA injections were introduced prior to and after the MPTP-injection in a mouse model of PD. Motor capabilities improved

Int. J. Mol. Sci. 2020, 21, 5982 10 of 25 in the MPTP-treated + TUDCA groups in comparison to MPTP-treated mice along with the ability to initiate movements and amend tremors. Parkin levels, an E3 ubiquitin ligase associated with mitochondrial biogenesis, were decreased in MPTP-treated mice and were attenuated in mice treated with TUDCA prior to MPTP [ 89 ]. This same group looked into dopaminergic cell death, oxidative stress and reactive oxygen species (ROS), using the same MPTP-induced PD mouse model. SH-SY5Y cells were treated with 1-methyl-4-phenylpyridinium (MPP+) or doxycycline for two in vitro PD

models, displaying TUDCA’s antioxidant qualities in both by preventing ROS production and lipid peroxidation through increased nuclear factor erythroid 2 related factor 2 (Nrf2) expression. TUDCA’s neuroprotective potential was replicated in vivo with the MPTP-induced mouse model, reverting ROS

production caused by MPTP and increasing the expression of Nrf2 and Nrf2 downstream cytoprotective enzymes, glutathione peroxidase and heme oxygenase-1 [90]. Lastly, a rotenone-induced PD model using rats with daily intraperitoneal injections of UDCA resolved striatal dopamine content close to

the control group level and significantly downregulated nuclear factor-κB (NF-κB), BCL2 associated X apoptosis regulator (Bax) and caspase-9 mRNA levels. Striatal TNF-α and IL-1β levels that were significantly increased in the rotenone-treated group were attenuated in the UDCA administered group. Additionally, this UDCA treatment reduced rotenone-induced alterations of striatal neuron mitochondrial and increased striatal ATP to 2-fold above the control values [ 91 ]. PD research

implementing bile acid-mediated therapeutics has attenuated several harmful cellular mechanisms of this disease state."

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Tauroursodeoxycholic Acid (TUDCA): A Promising Neuroprotective Agent Derived from Bile Salts 2021 restorativemedicine.org/dig...

"Orally ingested TUDCA is able to cross the blood-brain barrier to reach neuronal tissue and to prevent cell death.17 Evidence continues to mount in support of its potential clinical application as part of a therapeutic approach to the treatment of neuroinflammatory and neurodegenerative conditions."

I’ve mentioned this repeatedly but will give it another goUDCA is being trialed by Cure Parkinson’s

TUDCA Butyrate combo being trialed by Dr. Rudolph Tanzi and Brown students

Etc etc

I’ve included this in multiple threads so links are on here somewhere if interested

Bolt_Upright profile image
Bolt_Upright in reply to

Yes you have. The trial is using Sodium Phenylbutyrate, which is a prescription drug and not Sodium Butyrate:

"Sodium Phenylbutyrate is the sodium salt of phenylbutyrate, a derivative of the short-chain fatty acid butyrate, with potential antineoplastic activity. Phenylbutyrate reversibly inhibits class I and II histone deacetylases (HDACs), which may result in a global increase in gene expression, decreased cellular proliferation, increased cell differentiation, and the induction of apoptosis in susceptible tumor cell populations.

Sodium phenylbutyrate is the organic sodium salt of 4-phenylbutyric acid. A prodrug for phenylacetate, it is used to treat urea cycle disorders. It has a role as a prodrug, an EC 3.5.1.98 (histone deacetylase) inhibitor, a neuroprotective agent, an orphan drug and a geroprotector. It contains a 4-phenylbutyrate."

Not to be conspiratorial, but Dr Freed had what looked to be a successful PD trial using phenylbutyrate going, and then the money dried up. Phenylbutyrate is an orphan drug. I don't think there is any money in it. Now they are combining phenylbutyrate with TUDCA so it is a new compound. Just thinking.

in reply toBolt_Upright

YepI’ve had the same conclusion

And CP is likely using UDCA bc it’s prescription

Are there any other bile salts to consider? Have you read about slippery elm? I don’t know enough to form an opinion

Bolt_Upright profile image
Bolt_Upright in reply to

Sorry, no idea. I am glad I added TUDCA back to my stack. I think I will do 250 mg twice a day (with my 2 meals).

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Bolt_Upright

This company is trialing a combination of sodium phenylbutyrate and TUDCA: Amylyx Pharmaceuticals: Targeting Multiple Destructive Pathways To Reduce Neuronal Death seekingalpha.com/article/44...

I can't get sodium phenylbutyrate (but I can get sodium butyrate [who knows if they are similar]).

take bile salt supplements with taurine which can also help restore healthy bile formation. betaine which is an amino acid created by choline that works in combination with glycine, another amino acid. (From my notes)

Betaine is also called TMG

Bolt_Upright profile image
Bolt_Upright in reply to

One nice thing, Betaine is cheap. I could get it in this combo probiotic: walmart.com/ip/Spring-Valle...

in reply toBolt_Upright

It is recommended to take TMG if taking NMN to restore methylation I don’t know how that works biologically but it’s what I’m doing

What are you currently doing for probiotics? I’m still using Mathew’s that you recommended

Bolt_Upright profile image
Bolt_Upright in reply to

I take 3 probiotics:

1: S Boulardii (I just take one a day).

2: Yakult (I just have one bottle. I am going to start making yogurt with it).

3: Dr. Matthew.

in reply toBolt_Upright

healthunlocked.com/cure-par...

Restore Gold has TUDCA

Bolt_Upright profile image
Bolt_Upright in reply to

Yes, but Restore Gold is outside of my budget :)

Poor House :)
in reply toBolt_Upright

I just like to look at the ingredients It validates my choices 😊

Bolt_Upright profile image
Bolt_Upright in reply to

Yes! AND, we get to decide our own dosing and schedule!

Sydney75 profile image
Sydney75 in reply toBolt_Upright

I looked into restore gold too for my HWP. I was surprised to see the it is taken with meals bc one of the ingrediants is NAC which I have always been advised to take on an empty stomach for best absorption. If they price went down and # of pills needs might consider it again.

Looking for your iron chelator threadWhere is it?! (Long day)

Sorry to derail

Quercitin, grape seed extract, EGCG and Ligustrazine

ncbi.nlm.nih.gov/labs/pmc/a...

Our determination is going to pay off Bolt.

I’m starting a 3 day fast right now

I’m grumpy but determined. ☺️

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Bolt_Upright in reply to

I am tempted to start a fast also, but I am not mentally prepared :)

Inositol hexaphosphate: A natural iron chelator that may protect dopamine neurons

healthunlocked.com/cure-par...

Sydney75 profile image
Sydney75

I realize there is no $$ in supplements compared to prescription drugs, but certainly there must be some compassionate MDs who can make recommendations other than mucana. They seem so reluctant to make recommendations other than Mediter. Diet. It all get so confusing I cross check everything, I and try to purchase the supplements that have the most potential for improving or stalling the progression of PD. I have read about Tudac currently using Butylate (sp) and HWP is taking the PS128 probiotic. I think his came from his gut (second brain) MD said based on genetic testing his is idiopathic, not a farmer etc.

I am going to post a 164 pg PDF by Dr. Wahls, her emphasis is MS but she speaks about PD and neurodegeneration too.

Boscoejean profile image
Boscoejean

What does sodium phenylbutyrate treat?

Sodium phenylbutyrate is used together with a proper diet to help treat urea cycle disorders (including a specific liver enzyme deficiency) that help remove ammonia (nitrogen) from the body.Feb 1, 2022

Bolt_Upright profile image
Bolt_Upright in reply toBoscoejean

Interesting. Ammonia as a Potential Neurotoxic Factor in Alzheimer's Disease 2016 frontiersin.org/articles/10...

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