I wasn't aware of the enormous amount of studies you point out about synuclein. As many scientists sense and are investigating, this is one of the key points of Parkinson's. But no less so than the dysfunction of the mitochondria. And they are possibly related (internal and external toxins: pesticides, homocysteine, cortisol?).

I realized a few years ago that sometimes when studies don't appear in search engines like Pubmed (perhaps because there are few searches in that direction or because of the algorithms), books come to help us in those gaps.

Magnesium in Parkinson’s disease: an update in clinical and basic aspects - Magnesium in the Central Nervous System - NCBI Bookshelf

In one of them I found Oyanagi's 2010 study with magnesium and MPTP in mice. It was impossible for the group that received the highest dose of magnesium to provoke the experimental parkinsonism with MPTP. And I kept looking and found that in 2002, Golts had published a study on the ability of magnesium to inhibit alpha-synuclein aberration, both spontaneous and iron.

Later, something similar happened to me with green tea and its main polyphenol, EGCG. Xu's 2016 study was the only one I knew of.

Magnesium and green tea. But in recent years, many studies have come out that shed light on the whole world of Parkinson's: also vitamin C, astaxanthin, glutathione, vitamin K, vitamin B12, etc.

Possibly the same cellular "environment" that produces neuronal death, is the one that damages the mitocondria and produces the "madness" or aberration of alpha-synuclein. Oxidation, inflammation, elevated homocysteine? All together?

Green tea, magnesium or vitamin C act on all the possible mechanisms that produce degeneration in Parkinson's: oxidation, inflammation, homocysteine, alpha-synuclein, etc.

And "curiously" they all prevent or reduce the risk of Parkinson's and delay or stop the disease from getting worse.


1) Magnesium:

* Golts (2002). Magnesium inhibits spontaneous and iron-induced aggregation of alpha-synuclein. J Biol Chem.


2) Green Tea (EGCG polyphenol) -and also protects from damage produced by rotenone, paraquat...-.

Lorenzen (2014). How Epigallocatechin Gallate Can Inhibit α-Synuclein Oligomer Toxicity in Vitro. J Biol Chem

* Xu (2016). Epigallocatechin Gallate (EGCG) Inhibits Alpha-Synuclein Aggregation: A Potential Agent for Parkinson's Disease. Neurochem Res.

* Roy (2017). Suppression, disaggregation, and modulation of γ-Synuclein fibrillation pathway by green tea polyphenol EGCG. Protein Sci.

Yang (2017). EGCG-mediated Protection of the Membrane Disruption and Cytotoxicity Caused by the 'Active Oligomer' of α-Synuclein. Nature.

Singh (2011). Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochem. Pharmacol.

* Bieschke (2010). EGCG remodels mature α-synuclein and amyloid-β fibrils and reduces cellular toxicity. Proc. Natl. Acad. Sci. USA.


3) Glutathione.

* Seung (2003). Oxidized glutathione stimulated the amyloid formation of α-synuclein. FEBS Letters.

Jewett (2018). Glutathione S-Transferase Alpha 4 Prevents Dopamine Neurodegeneration in a Rat Alpha-Synuclein Model of Parkinson's Disease.
Front. Neurol

Trinh (2008). Induction of the Phase II Detoxification Pathway Suppresses Neuron Loss in Drosophila Models of Parkinson's Disease. J Neurosci.

* Koo (2013). α-Synuclein-mediated defense against oxidative stress via modulation of glutathione peroxidase. Biochim Biophys Acta.


4) Vitamin B6 and B2.

Pyridoxine is key in the sense that glutathione and magnesium are, since it stimulates glutathione synthesis and improves magnesium assimilation (somewhere I read, but I have not been able to rescue the quote, that brings magnesium to the interior of the neuron).

Wei (2020). Pyridoxine induces glutathione synthesis via PKM2-mediated Nrf2 transactivation and confers neuroprotection. Nature.

Pouteau (2018). Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial. PLoS One.

Abraham (1981). Effect of vitamin B-6 on plasma and red blood cell magnesium levels in premenopausal women. Ann Clin Lab Sci.

Schuchardt (2017). Intestinal Absorption and Factors Influencing Bioavailability of Magnesium–An Update. Curr Nutr Food Sci.


Riboflavin. And since vitamin B2 activates B6, I am not surprised by the results of studies on how riboflavin prevents Parkinson's by 50% (McCormick 1988) and improves motor skills by 44-71% (Coimbra 2003).


5) Vitamin B12.

Jia (2019). Vitamin B12 inhibits α-synuclein fibrillogenesis and protects against amyloid-induced cytotoxicity. Food and Function.

6) Vitamin C.

Khan (2012). Effect of L-ascorbic Acid on the climbing ability and protein levels in the brain of Drosophila model of Parkinson's disease. Int J Neurosci.

Wang (2010). Redox reactions of the α-synuclein-Cu(2+) complex and their effects on neuronal cell viability. Biochemistry.


7) Possible link between Homocysteine and alpha-synuclein.

Enomoto (2019). Alpha-synuclein phosphorylation by homocysteine. Alzheimer's and Dementia

https://aanddjournal.net/article/S15...19)30853-2/pdf


8) Vitamin K:

Silva (2013). Vitamins K interact with N-terminus α-synuclein and modulate the protein fibrillization in vitro. Exploring the interaction between quinones and α-synuclein. Neurochem Int.

9) Astaxanthin:

Wang (2018). Reversal of homocysteine-induced neurotoxicity in rat hippocampal neurons by astaxanthin: evidences for mitochondrial dysfunction and signaling crosstalk. Cell Death Discov.


10) Baicalein (fungal flavonoid):

Zhu (2004). The flavonoid baicalein inhibits fibrillation of a-synuclein and disaggregates existing fibrils. J. Biol. Chem.


Numerous substances that function as antioxidants, anti-inflammatories, protectives of alpha-synuclein integrity, regulators of the neurotoxic homocysteine, are known to prevent or reduce the risk of Parkinson's, have anti-Parkinsonian epigenetic activity, improve motor and non-motor symptoms, slow down or stop the disease. Magnesium depends on B6, B6 on B2 and so on an endless chain of the fascinating mechanism of neuroprotection of the human body, which fails against the multiple degenerative factors in the disease. And it seems to me that they point to Parkinson's not only as multifactorial but also as multicarential (both obvious and subclinical deficiencies). Even if the recommended amount is consumed, as is the case with homocysteine, because the body "consumes" vitamin B9 (and B6 and B12) in an attempt to reduce its level.