Connect the dots » HOPE Shortcut
The Gordian knot of Parkinsons and clues that helps us solve it.
Source: Connect the dots » HOPE Shortcut
The Stanford/Dr Tass, Vibration glove treatment for PD
Introduction
discussuion on reddit
Any thoughts on the Vibration Gloves?
by u/cicla in Parkinsons
few notes
according to the video, the glove treatment is very affective, some results show after 1 day, at least for some people the effect of symptom reduction is amazing, this suggest that the cause of symptoms was not massive dopaminergic cell death but instead, dysregulation of dopaminergic cells that disrupted dopamine production
the developer of the treatment looks at the problem (PD..dopaminergic cells not releasing dopamine) from a systems perspective, and develop a way to reset existing dysregulation (or more specifically disrupt synchronization – a process in which one cell type sync other cell types, to behave like it )
it’s a way to reboot/restart to prevent accumulation of processing errors. actually it’s more targeted then a general restart. Maybe Electroconvulsive therapy, more suitable “reset” option ..some evidence >>
for example, you can solve most Windows errors simply by rebooting it. If you had to dive into some window issue (e.g. computer hanging, slow, printer messed, weird error message, apps installed don’t work..) well, not a realistic goal
so, when looking at parkinson’s from a system approach perspective, a good start would be to find a way to reboot you system
this will not solve all issues, e.g. if you got PD from exposure to a toxin rebooting your system will not to much
same with windows, if you got a computer virus and it’s causing issue. a reboot might not be sufficient
but in case a particular sequence of events is not handled well by the system and cause an error situation with lasting effect.. reboot might help as long as you don’t repeat that sequence
in my case, many years ago, I lost my sense of smell, at the time, I theorized that my intuition took over some of the neurons dedicated to the processing of smell, intuition was one of my mostly used “modules” ( see Meir Briges type classifier, this personality type classification is based on identifying the main modules used’ e.g thinking/sensing/feeling/intuiting)
MTOR activation may reduce dophamin/l-dopa concentration in the brain
according to chatgpt, MTOR activation may reduce brain concentration of dopamine/l-dopa, some suggested mechanism of action is mentioned below
does MTOR affect l-dopa transfer in the BBB?
ChatGPT
The mammalian target of rapamycin (mTOR) is a protein kinase that regulates various cellular processes, including protein synthesis, cell growth, and autophagy. Meanwhile, levodopa (L-DOPA) is a medication commonly used to treat Parkinson’s disease. It is converted to dopamine in the brain, where it acts as a neurotransmitter.
There is some evidence suggesting that mTOR activation in the brain may influence the transport of L-DOPA across the blood-brain barrier (BBB). In a study published in the journal Nature, researchers found that mTOR inhibition with rapamycin increased the transport of L-DOPA across the BBB in mice, suggesting that mTOR may play a role in regulating the transport of L-DOPA into the brain (Carvey et al., 2011).
However, it should be noted that the exact mechanism by which mTOR affects L-DOPA transfer in the BBB is not yet fully understood, and further research is needed to elucidate this relationship. Additionally, the findings from animal studies may not necessarily apply to humans, and clinical studies are needed to determine the relevance of these findings to human disease.
User
how MTOR activation influence the transport pf l-dopa accross the blood brain barier?
ChatGPT
The exact mechanism by which mTOR activation influences the transport of L-DOPA across the blood-brain barrier (BBB) is not fully understood, but there are several hypotheses.
One possible mechanism is that mTOR activation may increase the expression and activity of efflux transporters in the BBB, which can decrease the uptake of L-DOPA into the brain. Efflux transporters are proteins that pump substances out of the brain and back into the bloodstream, and they play a critical role in regulating the transport of drugs and other substances across the BBB. Studies have shown that mTOR activation can upregulate the expression and activity of efflux transporters such as P-glycoprotein (P-gp), which can limit the uptake of L-DOPA into the brain (Bickel et al., 2015; Tai et al., 2015).
Another possible mechanism is that mTOR activation may increase the activity of enzymes that metabolize L-DOPA in the brain, which can decrease the availability of dopamine and limit the therapeutic efficacy of L-DOPA. For example, mTOR activation has been shown to increase the expression and activity of catechol-O-methyltransferase (COMT), an enzyme that metabolizes dopamine and L-DOPA (Jiang et al., 2016).
It’s worth noting that the relationship between mTOR activation and L-DOPA transport across the BBB is complex and may depend on various factors such as the dose and duration of treatment with mTOR inhibitors. Further research is needed to fully understand the mechanisms underlying this relationship.
User
so what trigger activation of MTOR
ChatGPT
mTOR activation is triggered by a variety of cellular signals, including growth factors, nutrients, energy status, and stress.
One of the primary activators of mTOR is insulin-like growth factor 1 (IGF-1), a hormone that is released in response to growth hormone and plays a key role in regulating growth and development. Other growth factors, such as epidermal growth factor (EGF) and fibroblast growth factor (FGF), can also activate mTOR.
Nutrients such as amino acids, glucose, and lipids can also stimulate mTOR activation. In particular, the amino acid leucine is a potent activator of mTOR. When amino acid levels are high, mTOR is activated and stimulates protein synthesis and cell growth.
Energy status also plays a role in mTOR activation. When cellular energy levels are high, as indicated by high levels of ATP and low levels of AMP, mTOR is activated. Conversely, when energy levels are low, as indicated by low levels of ATP and high levels of AMP, mTOR is inhibited.
Finally, stress signals such as oxidative stress, DNA damage, and hypoxia can also activate mTOR. These signals can lead to the activation of downstream pathways that stimulate mTOR, promoting cell survival and adaptation to stress.
It’s worth noting that the precise mechanisms by which these signals activate mTOR are complex and not fully understood. Further research is needed to fully elucidate the pathways involved in mTOR activation.
Effective Management of “OFF” Episodes in Parkinson’s Disease: Emerging Treatment Strategies and Unmet Clinical Needs
Vitamin B1 mega dose for PD
Photobiomodulation – Near infra red 10,070 light thearphy for PD
Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study >> .. n=12, all improved significantly, NIR (near infra red 10,070)
mechanism of action – boost mitochondria
PD meds in clinical trial (infographic)
Ambroxol as a Disease-modifying Treatment in GBA-PD – Full Text View – ClinicalTrials.gov
Ambroxol as a Disease-modifying Treatment in GBA-PD – Full Text View.
Source: Ambroxol as a Disease-modifying Treatment in GBA-PD – Full Text View – ClinicalTrials.gov
Radical new therapy for Parkinson’s will use stem cell transplants
Lab-grown nerve cells will replace those destroyed by disease – scientists hope treatment may be available in five years
Source: Radical new therapy for Parkinson’s will use stem cell transplants
PD – Reduce Alpha-synuclein level, experimental protocol
Misfolded Alpha synuclein protein accumulate into aggregates (oligomers) and damage host cell. PD patients brain cells tend to express alpha synuclein in large amounts, Alpha-synucleinis assumed to have a role in the disease process, reducing Alpha-synuclein level may prevent neuron death and delay or reverse the disease process More information >> [20]
The goal here is to normalize Alpha-synuclein level by using a simple protocol
Some notes:
- Evidence is limited
- Most references to the available evidence, is to scientific articles/research
- Some “how to” information on healthline.com also linked to aid implementation
- The challenge – decision making under conditions of uncertainty (meaning – evidence is partial, what do you do?).
- The solution (hopefully) – use a collection of tools, each with limited evidence, while probably not all work, most likely some will work
The protocol:
1 – Sweating – 3 liters/day or so, research show that Alpha-synuclein accumulate around sweat glands, it seems safe to assume that Alpha-synuclein is secreted via the sweat glands [18], [1]
2 – Alpha-synuclein is also secreted in the urine, so you can detox by drinking a lot and using mild diuretics e.g. parsley [2]
3 – Probiotics Bacillus Subtillis PXN21, “eats” Alpha-synuclein in the gut, this probiotics is in the market for a number of years, it’s probably safe Successful experiment in animal model(worms) [3].
Note: several bacteria species ( Lactobacillus and Enterococcus) interact with Levodopa ,and so , limit production of dopamine in the brain
4 – Optimise detox at the cell level (from the cell, out), raise glutathione level ( intravenous or suppository glutatyon or eat the precursors e.g sulfur found in eggs and cruciferous vegetables).
Glutathione has other benefits( master detoxifier, master anti oxidant), so it’s a good idea to boost it anyway [19].
How to increase glutathione by Mark Hayman [17]
More ways to increase glutathione [4].
5 –
Sleep issues may have an adverse effect on brain detox processes, in particular on alpha synuclein clearance [6].
Most of the brain detox is done by the Glymphatic System during sleep, give it time, 7-8 hours of sleep, don’t go to sleep to late. More information [7].
6 – Improve autophagy by intermittent fasting, preferably keto-fast – meaning a ketogenic diet in a 12 hours or less, daily eating window Ketogenic diet induced autophagy [8].
7- Alpha synuclein is found in Vertebras e.g cow, pig, chicken. Those molecules are almost identical to the human Alpha-synuclein, but not 100% identical, and may have a role in creating a pathology, much like in prion infection, more information >>[9].
Consider avoiding vertebrates, especially brain, bone merrow, bone broth.
Eggs – OK, as far as I checked.
8 – Mannitol
Mannitol was shown to inhibit formation of Alpha-synuclein oligomers[10], and there are anecdotal improvement reports of PD patients.
A clinical experiment (n=36) did not show significant improvement
You can add Mannitol to your diet in the dosage used in the experiment – start with 2.5 gram 2 times a day, gradually increase to 9 grams 2 times a day.
Why use Mannitol if the experiment showed no improvement ?
If, for example, subjects have existing damage(accumulated before the experiment), but new damage build up is slowed by say 50%, that’s very good, but the subjects will not experience any improvement. Maybe after a long time, difference relative to the control group will begin to show
9 – HSP – Heat shock proteins
Heat shock proteins – are listed here as they slow down or inhibit the formation of Alpha-synuclein oligomers.
The level of HSP in the body rise in response to adverse conditions (ice bath, sauna…intense exercise)
Sulforaphane- a compound found mostly in broccoli sprouts, also increase level of HSP. Sulforaphane is available in supplement form
Sulforaphaneis also beneficial to brain health as it reduces inflammation, increase anti oxidant activity and more [13], so it’s a good idea to use it anyway.
Mannitol also increase HSP level, this is one of the suggested mechanisms of action that explain why it inhibits creation of Alpha-synuclein oligomers, and generally improves PD [11].
More information on Sulforaphane >>
[13]
HSP27 binds Alpha synuclein >>[14]
and
Sulforaphane increase level of HSP27 >> [15]
also Sulforaphane increase level of HSP70 >>
[16]
10 – High intensity exercise
Irisin, a hormone secreted into the blood during high endurance and aerobic exercise, reduces levels of alpha-synuclein and restores movement in mouse models of PD [22]
Clinical research showing beneficial effect of high intensity exercise in PD patients [23]
11 – Ambroxol – an over-the-counter cough syrup
One of the major genetic risk factors believed to contribute to the development of PD is having a mutation in the gene called GBA1 (glucocerebrosidase). Unable to do its job correctly, this damaged gene leads to the build-up of unhealthy, misfolded clumps of alpha-synuclein in the brain. These clumps, called Lewy bodies, impact dopamine production and are the hallmark of PD.
A 2020 study published in JAMA Neurology, titled, “Ambroxol for the Treatment of Patients with Parkinson Disease with and Without Glucocerebrosidase Gene Mutations: A Nonrandomized, Noncontrolled Trial” (Mullin et al., 2020), investigated whether an over-the-counter cough syrup, called Ambroxol, may be the key. [24]
12 – Mega dose, Vitamin B1 (Thiamine),
Vitamin B1, especially in high dose, improve PD status according to a number of studies, one mechanism of action is reduction of Alpha-synuclein [24]
What to expect ?
If there is existing damage, and the protocol manage to stop/delay/reduce further damage, e.g. by 100%, this would be a significant achievement, but will not show as reduced symptoms (assuming n=1, meaning you tried it on yourself and you don’t have a control group etc).
A healthy person loose about 1% of its dopaminergic neurons every adult year, this will not present symptoms as symptoms start showing when 80% or more of the dopaminergic capacity is gone
Not saying this to discourage, I believe the protocol worth the effort, and can by you time. I believe solutions based on gene therapy and stem cell technology will be available soon.
Measuring Alpha-synuclein level require biopsy, we don’t have this technology available, but based on what we know from animal models, the protocol should work, at list some of it.
Besides it’s effect on Alpha-synuclein, the protocol is expected to improve brain health through several mechanisms including reduced inflammation, normalizing heavy metals and other toxins, reduce oxidative stress, improved insulin sensitivity… So…good idea to try it anyway.
One more thing, a quote from coacher Tony Robins –
Take Massive Action
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Guy
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Note:
This TED talk ___ suggests that misfolded alpha-synuclein aggregates are not a problem as long as normal alpha-synuclein is abundant, is this claim is correct, the above protocol should be avoided
I collected the above set of tools, as they directly affect alpha-synuclein. Nevertheless, most those are very popular general health tools e.g IM fasting, Keto, detox, sleep cycle compatible with circadian rhythm, Glutathione, Heat shock protein…
So, since they are popular, they seem to be safe.
[1] –
Gibbons, C. H., J. Garcia, N. Wang, L. C. Shih, and R. Freeman, 2016, The diagnostic discrimination of cutaneous α-synuclein deposition in Parkinson disease: Neurology, v. 87, no. 5, p. 505–512, doi:10.1212/wnl.0000000000002919.
[2] –
Giri, B., M. Seamon, A. Banerjee, S. Chauhan, S. Purohit, J. Morgan, B. Baban, and C. Wakade, 2021, Emerging urinary alpha-synuclein and miRNA biomarkers in Parkinson’s disease: Metabolic Brain Disease, v. 37, no. 6, p. 1687–1696, doi:10.1007/s11011-021-00735-2.
[3] –
Probiotic Bacillus subtilis Protects against α-Synuclein Aggregation -, 2022: <healthlinks.cc/probiotic-bacillus-subtilis-protects-against-%ce%b1-synuclein-aggregation/> (accessed October 6, 2022).
[4] –
Berkheiser, K., 2018, 10 Natural Ways to Increase Your Glutathione Levels: Healthline Media: <www.healthline.com/nutrition/how-to-increase-glutathione#TOC_TITLE_HDR_4> (accessed October 6, 2022).
[5] –
Perfeito, R., M. Ribeiro, and A. C. Rego, 2016, Alpha-synuclein-induced oxidative stress correlates with altered superoxide dismutase and glutathione synthesis in human neuroblastoma SH-SY5Y cells: Archives of Toxicology, v. 91, no. 3, p. 1245–1259, doi:10.1007/s00204-016-1788-6.
[6] –
Sundaram, S., R. L. Hughes, E. Peterson, E. M. Müller-Oehring, H. M. Brontë-Stewart, K. L. Poston, A. Faerman, C. Bhowmick, and T. Schulte, 2019, Establishing a framework for neuropathological correlates and glymphatic system functioning in Parkinson’s disease: Neuroscience & Biobehavioral Reviews, v. 103, p. 305–315, doi:10.1016/j.neubiorev.2019.05.016.
[7] –
Raypole, C., 2020, How to “Detox” Your Brain (Hint: It’s Easier Than You Think): Healthline Media: <www.healthline.com/health/brain-detox> (accessed October 6, 2022).
[8] –
Lindberg, S., 2018, Autophagy: What You Need to Know: Healthline Media: <www.healthline.com/health/autophagy#diet:~:text=In%20response%20to%20this%20restriction%2C%20your%20body%20will%20begin%20to%20start%20producing%20ketone%20bodies%20that%20have%20many%20protective%20effects.%20Khorana%20says%20studies%20suggest%20that%20ketosis%20can%20also%20cause%20starvation%2Dinduced%20autophagy%2C%20which%20has%20neuroprotective%20functions.> (accessed October 6, 2022).
[9] –
[10] –
Linetsky, E., S. Abd Elhadi, M. Bauer, A. Gallant, M. Namnah, S. Weiss, D. Segal, R. Sharon, and D. Arkadir, 2022, Safety and Tolerability, Dose-Escalating, Double-Blind Trial of Oral Mannitol in Parkinson’s Disease: Frontiers in Neurology, v. 12, doi:10.3389/fneur.2021.716126.
[11] –
Linetsky, E., S. Abd Elhadi, M. Bauer, A. Gallant, M. Namnah, S. Weiss, D. Segal, R. Sharon, and D. Arkadir, 2022, Safety and Tolerability, Dose-Escalating, Double-Blind Trial of Oral Mannitol in Parkinson’s Disease: Frontiers in Neurology, v. 12, doi:10.3389/fneur.2021.716126.
[12] –
[13] –
Sulforaphane, which is high in broccoli sprouts, clears away brain amyloid plaques and tau tangles and ameliorated memory defects in mice., 2019: <www.foundmyfitness.com/news/s/emuzn7/sulforaphane_which_is_high_in_broccoli_sprouts_clears_away_brain_amyloid_plaques_and_tau_tangles_and_ameliorated_memory_defects_in_mice/comments/gsmrq4#:~:text=To%20learn%20more,jed%2Dw%2Dfahey> (accessed October 6, 2022).
[14] –
Cox, D., D. R. Whiten, J. W. P. Brown, M. H. Horrocks, R. San Gil, C. M. Dobson, D. Klenerman, A. M. van Oijen, and H. Ecroyd, 2018, The small heat shock protein Hsp27 binds α-synuclein fibrils, preventing elongation and cytotoxicity: Journal of Biological Chemistry, v. 293, no. 12, p. 4486–4497, doi:10.1074/jbc.m117.813865.
[15] –
Gan, N., Y.-C. Wu, M. Brunet, C. Garrido, F.-L. Chung, C. Dai, and L. Mi, 2010, Sulforaphane Activates Heat Shock Response and Enhances Proteasome Activity through Up-regulation of Hsp27: Journal of Biological Chemistry, v. 285, no. 46, p. 35528–35536, doi:10.1074/jbc.m110.152686.
[16] –
Schepici, G., P. Bramanti, and E. Mazzon, 2020, Efficacy of Sulforaphane in Neurodegenerative Diseases: International Journal of Molecular Sciences, v. 21, no. 22, p. 8637, doi:10.3390/ijms21228637.
17-
Hyman, M., 2010, What is Glutathione and How Do I Get More of It? – Dr. Mark Hyman: <drhyman.com/blog/2010/05/12/what-is-glutathione-and-how-do-i-get-more-of-it/> (accessed October 9, 2022).
18-
Wang, N., C. H. Gibbons, J. Lafo, and R. Freeman, 2013, -Synuclein in cutaneous autonomic nerves: Neurology, v. 81, no. 18, p. 1604–1610, doi:10.1212/wnl.0b013e3182a9f449.
19-
Dringen, R., 2000, Metabolism and functions of glutathione in brain: Progress in Neurobiology, v. 62, no. 6, p. 649–671, doi:10.1016/s0301-0082(99)00060-x.
20-
Fields, C. R., N. Bengoa-Vergniory, and R. Wade-Martins, 2019, Targeting Alpha-Synuclein as a Therapy for Parkinson’s Disease: Frontiers in Molecular Neuroscience, v. 12, doi:10.3389/fnmol.2019.00299.
21-
Peters, R., 2006, Ageing and the brain: Postgraduate Medical Journal, v. 82, no. 964, p. 84–88, doi:10.1136/pgmj.2005.036665.
22-
23 –
Forced exercise 35% improvement, motor learning ? upregulate dopamine
24 – Ambroxol
www.parkinson.org/blog/science-news/ambroxol
25 – Vitamin B1
MSC Stem cell treatment in Panama
It must be done in Panama, as there are regulatory issues in other places
The clinic
Carnivore diet
Mikhaila Peterson’s on TEDX
carnivore.diet/ – Shawn Baker MD
Self reported health status, mostly very positive, in 2029 people following the carnivore, good results/
pubmed.ncbi.nlm.nih.gov/34934897/#:~:text=Results%3A%20A%20total%20of%202029,or%20more%20often%20by%2085%25.
Dr Saladino carnivore diet –
www.amazon.com/Carnivore-Code-Unlocking-Returning-Ancestral/dp/B08FF4BSWJ/ref=sr_1_2?crid=SUH52F8ND70H&keywords=dr+saladino&qid=1659124365&sprefix=dr+sala%2Caps%2C284&sr=8-2
Mikhaila Peterson’s podcast
www.amazon.com/Carnivore-Code-Unlocking-Returning-Ancestral/dp/B08FF4BSWJ/ref=sr_1_2?crid=SUH52F8ND70H&keywords=dr+saladino&qid=1659124365&sprefix=dr+sala%2Caps%2C284&sr=8-2
Basal Ganglia Calcification – rare
WebMD explains what Basal Ganglia Calcification is.
The Parkinson’s Protocol™ By Jodi Knapp
The Parkinson’s Protocol – Natural Healing By Jodi Knapp. Clear Step by Step Instructions – Get The Parkinson’s Protocol For an Exclusive Discounted Price. Get it today (Recommended)
Source: The Parkinson’s Protocol™ By Jodi Knapp — Parkinsons Protocol by Jodi Knapp
Alpha-Synuclein in Parkinson’s Disease: From Pathogenetic Dysfunction to Potential Clinical Application – PMC
Alpha-Synuclein in Parkinson’s Disease: From Pathogenetic Dysfunction to Potential Clinical Application
Synucleinopathies – an overview | ScienceDirect
Synucleinopathies
Source: Synucleinopathies – an overview | ScienceDirect Topics
Vertebrate food products as a potential source of prion-like α-synuclein – PMC
Therapeutic Effects of Hydrogen in Animal Models of Parkinson’s Disease – PMC
Therapeutic Effects of Hydrogen in Animal Models of Parkinson’s Disease
Source: Therapeutic Effects of Hydrogen in Animal Models of Parkinson’s Disease – PMC
PBM – photobiomodulation for PD
In 2008, the researchers in Wisconsin, US discovered that PBM (photobiomodulation) is effective on Parkinson’s ( Liang et al., 2008 ). Click to view
Afterwards, researchers in Australia, France and Switzerland published numerous research studies that PBM can reduce the symptoms of MPTP and/or 6-OHDA and alpha-synuclein in the animal model with Parkinson’s (Johnstone et al., 2016 ). Click to view
In 2016, the study on PBM having an effect on monkey model with Parkinson’s has been published in the Annals of Neurology in the American Journal of Neurology. Click to view
In this study, optical fiber devices with visible red light (670 nm) were planted in the brain and MPTP injections were given for a week. In this treatment, the majority of monkeys reversed the symptoms. ( Darlot et al., 2016 ).
Red light (670 nm) was used in this study, but near-infrared light (810 nm) was also used in other studies. Usually light is administered either as a span or as a straight line to the head through percutaneous fibers, but one study suggests that it has a remote neurological protection effect on the brain and that photobiotics may be better represented. ( Johnstone et al., 2014 , Kim et al 2017 ).
Please click here to read more studies on PBM therapy and Parkinson’s
Source: PBM