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]

List of natural diuretics >>

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].

Note, the other direction, overexpression of Alpha synuclein cause a decrease in glutathione level [5].

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].

During sleep, glymphatic system activity is characterized by a 60% increase in the interstitial space and CSF flow (Jessen et al., 2015; Xie et al., 2013), and clearance of alpha-synuclein, along with other protein accumulations, from the brain (Iliff et al.,  2012[6].

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].

Different heat shock proteins bind α-Synuclein with distinct mechanisms and synergistically prevent its  amyloid aggregation

More information on Sulforaphane >>

HSP27 binds Alpha synuclein  >>[14]


Sulforaphane increase level of HSP27 >> [15]

also  Sulforaphane increase level of HSP70 >>

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

In a PD patient who started the protocol with say  15% of its dopaminergic capacity, even in the case of 100% cleanup of alpha synuclein, he will still be on 15% capacity and 14% next year, so…[21]

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


What do you think ? feedback welcome, please comment below

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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/&gt; (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&gt; (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&gt; (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.&gt; (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&gt; (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.


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/&gt; (accessed October 9, 2022).


‌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.


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.


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.


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Exercise Hormone Halts Parkinson’s Disease Symptoms

23 –

Forced exercise 35% improvement, motor learning ? upregulate dopamine

24 – Ambroxol


25 – Vitamin B1


The diagnostic discrimination of cutaneous α-synuclein deposition in Parkinson disease  

Results: Skin biopsies provide >90% sensitivity and >90% specificity to distinguish PD from control participants across all biopsies sites with quantification of either pilomotor or sudomotor α-synuclein deposition. All individuals with PD have significantly higher cutaneous α-synuclein deposition than control participants, even those individuals with PD and no evidence of autonomic dysfunction. Deposition of α-synuclein is most prominent in sympathetic adrenergic nerve fibers innervating the arrector pili muscles, but is also present in sudomotor (sympathetic cholinergic) nerve fibers. α-Synuclein is present even in the early stages of disease and disease of short duration. α-Synuclein ratios were higher in individuals with autonomic failure, with more advanced stages of disease and disease of longer duration.Conclusions: The α-synuclein ratio provides a sensitive and specific diagnostic biomarker of PD even in patients without autonomic failure.Classification of evidence: This study provides Class III evidence that cutaneous α-synuclein deposition accurately identifies patients with PD.

Source: The diagnostic discrimination of cutaneous α-synuclein deposition in Parkinson disease – PMC


  • So seems that sweat glands are secreting alpha-synuclein, could sweating be used to detox or to normalize levels of alpha-synuclein

probiotics Bacillus subtilis PXN® 21® eliminates alpha-synuclein aggregates, possible PD treatment

Article in Cell megazine:

where to buy:


Could α-Synuclein Inhibition be a Treatment for PD?

A 2020 publication in the MDPI journal, Biomolecules looks at targeting a-syn for PD therapeutics. PD is characterized by the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy Bodies (cytoplasmic inclusions). The Lewy Bodies are clumps of protein that can build up and create problems in the brain. The Lewy Bodies contain the aggregated a-synuclein protein that can propagate throughout the brain. Many PD studies have looked at ways of inhibiting a-synuclein accumulation to ease PD symptoms. There are various approaches to a-syn inhibition and multiple clinical trials that examine the link between PD and a-syn, with the hope that a treatment may be found for PD using a-syn. Given the central role of α-syn in PD pathology and progression, α-syn met the criteria to be a tantalizing and evident therapeutic target for PD. Promising strategies include predominantly immunization, anti-aggregative molecules, and an increase in α-syn clearance.

Source: Targeting α-Synuclein for PD Therapeutics: A Pursuit on All Fronts

Ridding Cells of Harmful Protein Aggregates by Inducing Autophagy

This short, enlightening video clip is an extract from a FoundMyFitness interview with Dr. Guido Kroemer. PD is characterized by protein aggregation of a-synuclein and mitochondrial dysfunction, partly due to mitophagy failure. A recently proposed strategy in preventing (or perhaps treating) neurodegenerative diseases like PD is to starve the cells or use biochemical methods to induce general autophagy and thus help the cell rid itself of protein aggregates. Here Dr. Kroemer describes how mitophagy contributes to the pathophysiology of neurodegenerative diseases like PD and Alzheimer’s and how autophagy might mitigate these processes.

Neuronal Autophagy and the Predisposition for PD

A study by Dr. Yue published by the Michal J. Fox Foundation tested the hypothesis that neuronal autophagy is critical for the regulation of alpha-synuclein protein levels and protective against neuronal death; dysfunction of autophagy predisposes to the pathogenesis of PD in dopamine neurons. This was done by establishing conditional knock-out mice in which an essential autophagy gene, Atg7, is deleted specifically in dopamine neurons. These pre-clinical models were used to investigate whether alpha-synuclein wildtype or PD-mutant A53T will be accumulated and deposited into Lewy body-like inclusions in the mutant dopamine neurons. In addition, they studied the effect of inactivation of autophagy on oxidative stress level, striatal dopamine content, and dopamine neuron degeneration. results suggest that neuronal autophagy is critical for the regulation of alpha-synuclein protein levels and protective against neuronal death; dysfunction of autophagy may predispose dopamine neuron to PD-like pathology.

Source: Autophagy in Dopamine Neurons: Clearance of Alpha-synuclein and Neuroprotection

PD and Autophagy Impairment in Synucleinopathy

A 2019 study published by NCBI discusses the active participation of autophagy impairment in alpha-synuclein accumulation and propagation, as well as alpha-synuclein-independent neurodegenerative processes in the field of synucleinopathy. There is genetic and post-mortem evidence suggesting that autophagy is involved in synucleinopathies. Also, studies demonstrate the role of autophagy in the pathology of synucleinopathy. α-syn is mainly degraded by both macroautophagy and chaperone-mediated autophagy. Thus, autophagy defects induce intracellular α-syn accumulation, participating in its aggregative state towards the formation of α-syn-positive intracytoplasmic inclusions. Plus, autophagy defects also increase the α-syn secretion by the non-autophagic exosomal pathway, leading to increased cell-to-cell transmission of the protein, and thus the propagation of the α-syn-linked pathology in different brain regions of the CNS. However, autophagy defects also cause detriment effects in cellular homeostasis: (i) lysosomal impairment through structural or functional defects leads to accumulation of non-degraded products and increased production of ROS; (ii) decreased mitophagy leads to neuronal bioenergetic imbalance, and (iii) defective cargo trafficking impairs the addressing of vesicles to lysosomal clearance. There is increasing evidence that inducing the autophagy pathways (by natural, chemical, or genetic approaches), has become a relevant therapeutic approach to counteract the deleterious effects of autophagy impairment in synucleinopathy.

Source: Autophagy in Synucleinopathy: The Overwhelmed and Defective Machinery

Corynoxine, isolated from Uncaria rhynchophylla, promotes the clearance of alpha-synuclein

Corynoxine, isolated from Uncaria rhynchophylla, promotes the clearance of alpha-synuclein

Corynoxine, isolated from Uncaria rhynchophylla, promotes the clearance of alpha-synuclein via mTOR pathway [R].

use of Uncaria rhynchophylla, known as “Gou-teng” herb extract



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