Hi, I have been a silent reader of this forum for many years. During the past couple of months, I often had to think about a study from Australia. There, it is said, that POTS (at least in a subgroup) is caused by an epigenetic malfunction of the NE-Transporter. This epigenetic malfunction can be removed in vitro by using an EZH2 inhibitor (GSK126). The EZH2 expression in POTS patients was about 70% higher compared to the healthy controls. The first EZH2 inhibitor (Tazemetostat) is available since this year for certain types of cancer.
https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.119.315654
In the consequence, I did some research, whether an overexpression of EZH2, could not only explain POTS, but other findings of ME/ CFS as well. I did find some very interesting points (at least in my opinion):
First of all, EZH2 is temporally upregulated during certain virus infections (including EBV):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262262/
In 2017, it was stated, that EZH2 inhibitors could, in the future, act as broadband antivirals:
https://mbio.asm.org/content/8/4/e01141-17
EZH2 upregulation leads to a pro-inflammatory state and mediates inflammation (including intestinal and mediates spinal neuroinflammation and neuropathic pain (in rats)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410968/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547712/
https://www.oarsijournal.com/article/S1063-4584(18)30443-6/fulltext
The absence of Ezh2 leads to reduced cytokine secretion and suppresses macrophage- dependent disease development. EZH2 inhibitors could even attenuate sepsis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940273/
https://pubmed.ncbi.nlm.nih.gov/31518916/
Steroidogenic Differentiation in the Adrenal Cortex is programmed by EZH2
https://pubmed.ncbi.nlm.nih.gov/30541888/
EZH2 overexpression leads to allergic inflammation and mast cell degradation (Mast Cell Activation Syndrome)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542604/
Very interesting to me is the role of EZH2 in the circadian clock function, as delayed sleep- phase-circle is a problem, many of us are facing.
https://www.jbc.org/content/281/30/21209.full
Ezh2 Regulates Differentiation and Function of Natural Killer Cells Through Histone Methyltransferase Activity
https://pubmed.ncbi.nlm.nih.gov/26668377/
Another interesting point to me is that EZH2 is located on chromosome 7. Other disorders associated with this chromosome are Ehlers-Danlos-Syndrome and Marfan-Syndrome. With both, there is a huge overlap with ME/ CFS.
So, I would find it very interesting if these findings from Australia could be replicated, not only in POTS, but in ME patients as well.
Given the fact that temporary EZH2 upregulation is normal in certain infections (e.g. EBV) etc., the question is (in case these findings can be replicated), why is EZH2 trapped at such a high level in patients? Probably, a gene that is faulty in certain connective tissue diseases, is responsible for down-regulation after the event in healthy persons?
Btw. some of the supplements, many of us are taking act as an EZH2 inhibitor (at least in vitro), including Omega3, broccoli. quercetin, curcumin.
https://europepmc.org/article/pmc/pmc4552355
In vivo, EZH2 down-regulation can be achieved by melatonin (concerning cancer in this study)
https://pubmed.ncbi.nlm.nih.gov/27121240/
I would be very interested in your opinion about this. Maybe, some of you have experiences with certain herbals or melatonin concerning general inflammation.
Greetings from Germany
Philipp
https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.119.315654
In the consequence, I did some research, whether an overexpression of EZH2, could not only explain POTS, but other findings of ME/ CFS as well. I did find some very interesting points (at least in my opinion):
First of all, EZH2 is temporally upregulated during certain virus infections (including EBV):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262262/
In 2017, it was stated, that EZH2 inhibitors could, in the future, act as broadband antivirals:
https://mbio.asm.org/content/8/4/e01141-17
EZH2 upregulation leads to a pro-inflammatory state and mediates inflammation (including intestinal and mediates spinal neuroinflammation and neuropathic pain (in rats)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410968/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547712/
https://www.oarsijournal.com/article/S1063-4584(18)30443-6/fulltext
The absence of Ezh2 leads to reduced cytokine secretion and suppresses macrophage- dependent disease development. EZH2 inhibitors could even attenuate sepsis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940273/
https://pubmed.ncbi.nlm.nih.gov/31518916/
Steroidogenic Differentiation in the Adrenal Cortex is programmed by EZH2
https://pubmed.ncbi.nlm.nih.gov/30541888/
EZH2 overexpression leads to allergic inflammation and mast cell degradation (Mast Cell Activation Syndrome)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542604/
Very interesting to me is the role of EZH2 in the circadian clock function, as delayed sleep- phase-circle is a problem, many of us are facing.
https://www.jbc.org/content/281/30/21209.full
Ezh2 Regulates Differentiation and Function of Natural Killer Cells Through Histone Methyltransferase Activity
https://pubmed.ncbi.nlm.nih.gov/26668377/
Another interesting point to me is that EZH2 is located on chromosome 7. Other disorders associated with this chromosome are Ehlers-Danlos-Syndrome and Marfan-Syndrome. With both, there is a huge overlap with ME/ CFS.
So, I would find it very interesting if these findings from Australia could be replicated, not only in POTS, but in ME patients as well.
Given the fact that temporary EZH2 upregulation is normal in certain infections (e.g. EBV) etc., the question is (in case these findings can be replicated), why is EZH2 trapped at such a high level in patients? Probably, a gene that is faulty in certain connective tissue diseases, is responsible for down-regulation after the event in healthy persons?
Btw. some of the supplements, many of us are taking act as an EZH2 inhibitor (at least in vitro), including Omega3, broccoli. quercetin, curcumin.
https://europepmc.org/article/pmc/pmc4552355
In vivo, EZH2 down-regulation can be achieved by melatonin (concerning cancer in this study)
https://pubmed.ncbi.nlm.nih.gov/27121240/
I would be very interested in your opinion about this. Maybe, some of you have experiences with certain herbals or melatonin concerning general inflammation.
Greetings from Germany
Philipp