Review: 'Through the Shadowlands’ describes Julie Rehmeyer's ME/CFS Odyssey
I should note at the outset that this review is based on an audio version of the galleys and the epilogue from the finished work. Julie Rehmeyer sent me the final version as a PDF, but for some reason my text to voice software (Kurzweil) had issues with it. I understand that it is...
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Increased nuclear factor-κB and loss of p53 are key mechanisms in ME/CFS

Discussion in 'Latest ME/CFS Research' started by jace, Aug 29, 2012.

  1. jace

    jace Off the fence

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    England
    http://www.medical-hypotheses.com/article/S0306-9877(12)00358-1/abstract

    Gerwyn Morris and Michael Maes unpick the difference between ME and CFS. I'm hoping for sight of the full paper soon.

    Abstract

    Fukuda’s criteria are adequate to make a distinction between Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS) and chronic fatigue (CF), but ME/CFS patients should be subdivided into those with (termed ME) and without (termed CFS) post exertional malaise [Maes et al. 2012]. ME/CFS is considered to be a neuro-immune disease. ME/CFS is characterized by activated immuno-inflammatory pathways, including increased levels of pro-inflammatory cytokines, nuclear factor κB (NF-κB) and aberrations in mitochondrial functions, including lowered ATP.
    These processes may explain typical symptoms of ME/CFS, e.g. fatigue, malaise, hyperalgesia, and neurologic and autonomic symptoms. Here we hypothesize that increased NF-κB together with a loss of p53 are key phenomena in ME/CFS that further explain ME/CFS symptoms, such as fatigue and neurocognitive dysfunction, and explain ME symptoms, such as post-exertional malaise following mental and physical activities. Inactivation of p53 impairs aerobic mitochondrial functions and causes greater dependence on anaerobic glycolysis, elevates lactate levels, reduces mitochondrial density in skeletal muscle and reduces endurance during physical exercise.
    Lowered p53 and increased NF-κB are associated with elevated reactive oxygen species. Increased NF-κB induces the production of pro-inflammatory cytokines, which increase glycolysis and further compromise mitochondrial functions. All these factors together may contribute to mitochondrial exhaustion and indicate that the demand for extra ATP upon the commencement of increased activity cannot be met. In conditions of chronic inflammation and oxidative stress, high NF-κB and low p53 may conspire to promote neuron and glial cell survival at a price of severely compromised metabolic brain function. Future research should examine p53 signalling in ME/CFS.
     
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  2. Sherlock

    Sherlock tart cherry etc. for joints, insomnia

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    Czechosherlockia, USA
    I remember that p53 is used as a prognostic indicator in certain cancers. Another was ki-67- so without looking, I'd guess that has also been looked at in CFS. mTOR would be another. What is wanted to be low in cancer is wanted to be high in CFS.
     
  3. Mula

    Mula Senior Member

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    I have not found a p53 paper for MECFS. Do you have one?
     
  4. alex3619

    alex3619 Senior Member

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    Logan, Queensland, Australia
    Hi Mula, here are three that mention p53. One of these, the last one, is in a table though - easier to find with a search. However, they did say that the p53 pathway is one of a number that is predictive of ME severity.

    http://www.hirou.jp/english/pdf/ikuta.pdf

    http://db.wdc-jp.com/cgi-bin/psj/data/bpb/pdf/201103/b03_0354.pdf

    http://www.bioinformation.net/006/97320630006120.pdf

    None of these papers are specifically about p53 however, the discussion arises with respect to other factors.

    Bye, Alex
     
  5. Mula

    Mula Senior Member

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    The paper is proposing a role for p53 but none of those studies or any other has taken a look at p53 levels, so there should be no expectation for p53 to not be similar to cancer levels.
     

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