Professor & patients' paper on the solvable biological challenge of ME/CFS: reader-friendly version
Simon McGrath provides a patient-friendly version of a peer-reviewed paper which highlights some of the most promising biomedical research on ME/CFS ...
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Unfolded Protein Response and A Possible Treatment for CFS

Discussion in 'General Treatment' started by mariovitali, May 3, 2015.

  1. mariovitali

    mariovitali Senior Member

  2. zippy


    Thanks Mario for your original post. I'm yet to read the entire thread.

    I ended up here while researching why ryegrass (with a parasitic fungus almost identical to tunicamycin, an inhibitor of of n linked glycolisation that I think you mentioned) causes me to vomit frequently while others who live nearby simply get hayfever or asthma symptoms from it (it's very bad this year). I also ended up with what I would call excitotoxicity last night so have been researching today to avoid it happening again. My research led me to glycolisation then UPR, and I found your post. I was interested in the correlations between your list of UPR impairment factors (methylation, choline, environmental toxins, homocysteine etc.) since I'm already addressing most of those due to chemical sensitivities and histamine issues (with success). So your post confirmed for me that it's all related. Maybe with just a bit more tweaking of my supplements I can get on top of it. Much appreciate that you shared, thanks!
    mariovitali likes this.
  3. Lolinda

    Lolinda Autoimmune POTS + axonal polyneuropathy

    Coffee helps against ER stress.

    I post the excerpt of the paper with some additional context:
    Regarding the mechanism by which coffee exerts its effects on steatosis and fibrosis, there is a quantity of convincing evidence that it is able to reduce the rate of fat and collagen deposition in the liver. In a rat model of fatty liver disease, we showed that animals fed with high-fat diet and decaffeinated coffee showed lower levels of hepatic fat and collagen, reduced liver oxidative stress, and improved liver inflammation and fibrosis.43,44 In a recent study, our group demonstrated that decaffeinated coffee consumption is able to modulate the expression of endoplasmic reticulum and mitochondrial chaperones both under standard diet and high-fat diet conditions. Among proteins upregulated by coffee consumption, there seems to be a particularly significant induction of the chaperone glucose-related protein 78 (GRP78), a master regulator of endoplasmic reticulum homeostasis, belonging to the heat shock protein 70 (HSP70) family. Consistent with GRP78 induction, coffee increases the expression of mitochondrial HSP70, which plays a pivotal role in endogenous antitumour defense against different cancers through activation of both innate and adaptive immune systems. In addition, coffee induces the expression of another chaperone called DJ-1, which plays a role in autophagy, and is also a redox-sensitive protein that scavenges reactive oxygen species by increasing glutathione synthesis. Finally, coffee induces the expression of antioxidant and stress sensor proteins, in particular peroxiredoxin 1 (PRDX1), which is able to catalyze the peroxide reduction of H2O2, organic hydroperoxides, and peroxynitrite. The PRDX1 induction leads to inhibition of JNK activation, which has been involved in NASH pathogenesis.45

    I post this because several people were interested in this topic:

    Reading this, I started drinking decaf coffee several times per day. I benefitted greatly.
    Last edited: Jan 16, 2017 at 9:21 AM
    eljefe19 and Gondwanaland like this.
  4. Lolinda

    Lolinda Autoimmune POTS + axonal polyneuropathy

    A question to everyone on this thread: how does misfolded protein response feel? How does improvement thereof feel?

    What I mean by these questions:
    Misfolded protein resonse is a cellular event. But having too much of it overall, or reducing its occurrence in the body could have some aspects that one can feel. So for example, if you tried remedies that are recommended on this thread, was there some common thing you felt with several of these?

    People on PR usually know me as a researcher posting more often than not scientific papers :). But I like a lot to look at how things feel. While feelings have obvious problems such as big variance among individuals, they also have great advantages such as fast feedback at home, without a lab.

    Are there any labs for measuring ER stress? I can imagine that some proteins associated with ER sress leak into the bloodstream and could be tested there...
    Last edited: Jan 16, 2017 at 3:29 PM

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