The 12th Invest in ME Research Conference June, 2017, Part 2
MEMum presents the second article in a series of three about the recent 12th Invest In ME International Conference (IIMEC12) in London.
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A New Potential Cause for Alzheimer’s: Arginine Deprivation (relevance for ME/CFS?)

Discussion in 'Other Health News and Research' started by MEDad, Apr 22, 2015.

  1. MEDad

    MEDad

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    Hello everyone. This will be my first post ever here at PR. I've been lurking here for a couple of months now after my teenage daughter got the diagnosis moderate to severe ME/CFS (ICC definition) five months ago.

    I came across this article yesterday that had me thinking a bit: A New Potential Cause for Alzheimer’s: Arginine Deprivation

    An executive summary with quotes (bold to enhance important keywords):

    "A new Duke University study in mice suggests that in Alzheimer’s disease, certain immune cells that normally protect the brain begin to abnormally consume an important nutrient: arginine. Blocking this process with a small-molecule drug prevented the characteristic brain plaques and memory loss in a mouse model of the disease"
    ...
    "The group did find CD11c microglia and arginase, an enzyme that breaks down arginine, are highly expressed in regions of the brain involved in memory, in the same regions where neurons had died.

    Blocking arginase using the small drug difluoromethylornithine (DFMO) before the start of symptoms in the mice, the scientists saw fewer CD11c microglia and plaques develop in their brains. These mice performed better on memory tests."

    The drug DFMO seems to be a arginase inhibitor drug. Having read several posts here about different peoples sometimes positive experiences with nitrate donors of different kinds, and thinking about the recently published patent from Fluge & Mella on nitrate donors I thought that this might be of relevance. Going back to look at the Fluge & Mella patent once more yesterday I find the following sentence:

    "Further, the skilled person is well aware of other compounds suitable to influence the NO level, e.g. by influencing the amount or level of available substrate for NO production. Examples thereof include compounds inhibiting arginase, e.g. arginase II, a competitor of the NO synthase (NOS)."

    I started searching for more information about arginase inhibition, and it seems to be a hot topic in other areas in life science research at the moment. I'll compile a list later. Meanwhile, let me know what you think.
     
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  2. Gingergrrl

    Gingergrrl Senior Member

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    @MEDad Sorry, I read this twice but can't grasp, is it saying that Arginine helped the mice brain or hurt it? In re: to Alzheimer's was it good or bad?

    I have been told by two doctors not to take Arginine b/c it increases herpes viruses and I am still IgM positive for EBV and VZV. This is why I always get confused how Arginine could help CFS.

    I am very interested in the Nitro part and it has helped me twice but often my BP is too low to take it (80's/50's) and it would be very dangerous. I'm hoping to keep learning more about this topic and thanks for posting it.

    I am sorry about your daughter and welcome to PR.
     
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  3. lansbergen

    lansbergen Senior Member

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    http://en.wikipedia.org/wiki/Eflornithine
    http://clincancerres.aacrjournals.org/content/5/5/945.long
    Development of Difluoromethylornithine (DFMO) as a Chemoprevention Agent1

    http://link.springer.com/article/10.1007/BF00179593
     
  4. Gingergrrl

    Gingergrrl Senior Member

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    So if Arginine can cause Alzheimer's and herpes viruses to replicate, why is it being recommended by some on PR for ME/CFS? Am I still missing something?
     
  5. MEDad

    MEDad

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    @Gingergrrl : A certain type of activated microglia produces too much arginase (not aginine). Arginase catalyses breakdown of arginine, leaving too little arginine for NOS to work properly.

    I'm sorry if the initial post was hard to understand. I guess I had too much I wanted to say (at once). The basic point was:

    Too much arginase (for some reason) => increased breakdown of arginine => not enough available arginine for proper NOS functioning.

    My thought was that instead of using arginine or nitrate supplements, arginase inhibition might be an alternative.
     
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  6. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    N-acetyl-L-cysteine (NAC)?
     
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  7. MEDad

    MEDad

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    Yes that seems to be one possibility. I haven't had time to research the different options regarding arginase inhibition.

    DFMO was the drug used in the mouse study I referred to above, but there is surely other and maybe better options(?).
     
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  8. adreno

    adreno PR activist

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    I wonder if this makes taking lysine a bad idea.
     
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  9. MEDad

    MEDad

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    nandixon and RustyJ like this.
  10. Hip

    Hip Senior Member

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    Hi MEDad

    Interesting findings.

    A few years ago I looked into arginase, but I sort of forgot about all the online research I did on this subject. However, I still have my notes.

    Arginase is often involved in immune evasion (immune evasion = the clever tactics that infectious pathogens use to thwart or disarm our immune system). Both bacteria and viruses make arginase for immune evasion purposes:

    Various bacteria either possess the genes to make arginase, or have means to up-regulate arginase. These bacteria use arginase to break down arginine, which in turn limits the immune system's production of the antimicrobial nitric oxide, allowing the bacteria to better survive in the body. See these studies:

    Helicobacter pylori arginase inhibits nitric oxide production by eukaryotic cells: a strategy for bacterial survival

    Arginase modulates Salmonella induced nitric oxide production in RAW264.7 macrophages and is required for Salmonella pathogenesis in mice model of infection

    Arginase-1 expression in granulomas of tuberculosis patients

    Modulation of the arginase pathway in the context of microbial pathogenesis: a metabolic enzyme moonlighting as an immune modulator

    Some viruses possess the ability to induce arginase, and again this is probably done to thwart the immune response by limiting the production of nitric oxide which the body uses to fight the virus.

    Human cytomegalovirus induces upregulation of arginase II: possible implications for vasculopathies


    Whether the above pathogens that mess around with our arginase has significance for ME/CFS, I don't know. For example, if you have cytomegalovirus in your body, does the arginase that it induces thwart the nitric oxide immune response such that the immune system now has trouble fighting viruses strongly linked to ME/CFS, such as coxsackievirus B, echovirus or Epstein-Barr virus?



    In any case, whether or not arginase is increased in ME/CFS by such pathogens, reducing arginase in order to try to produce more nitric oxide so as to combat the viruses found in ME/CFS, such as coxsackievirus B, echovirus or Epstein-Barr virus might be worth trying.

    As you mentioned, norvaline reduces arginase (and this can be bought at places like purebulk.com).

    And a compound in rhubarb called piceatannol reduces arginase, and increases nitric oxide (see here).



    There is also another enzyme that breaks down arginine called arginine dihydrolase.
     
    Last edited: Apr 23, 2015
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  11. MEDad

    MEDad

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    I've been reading a bit more about arginase inhibition. Seems the most effective easily available supplements are BCAA (branched chain amino acids), norvaline, and citrulline, based on lab tests.
     
    Hip likes this.
  12. Hip

    Hip Senior Member

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    @Mary might be interested in this: she found BCAAs greatly reduced her PEM and crashing, though the mechanism appears to be related to the serotonin inhibition of BCAAs.
     
    MEDad likes this.
  13. Mary

    Mary Senior Member

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    I also read that the amino acid ornithine is an arginase inhibitor. The drug DFMO, which appears to be a synthetically modified form of ornithine from its name (I have no idea of the chemistry involved), is mentioned above as an inhibitor, but I'm just wondering if the amino acid ornithine would be safer and cheaper to take, and quite possibly just as effective if not more so. Drug companies often alter natural substances in order to patent them and make money, sometimes to our detriment.
     
    MEDad likes this.
  14. Mary

    Mary Senior Member

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    Thanks, Hip - I didn't see this post. Very interesting --- perhaps the BCAAs are helping in more than one way.
     
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  15. Tunguska

    Tunguska Senior Member

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    Yeah and I was thinking dairy, since it's so high in lysine, especially whey. Then again people were taking whey for the glutathione with results as I understand. I find it highly confusing. Though clearly lysine lowers some form of NOS from all I read.
     

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