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The Deleterious Effects of Oxidative and Nitrosative Stress on Palmitoylation, Membrane Lipid Rafts

Discussion in 'Latest ME/CFS Research' started by JaimeS, Sep 3, 2015.

  1. JaimeS

    JaimeS Senior Member

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    The Deleterious Effects of Oxidative and Nitrosative Stress on Palmitoylation, Membrane Lipid Rafts and Lipid-Based Cellular Signalling: New Drug Targets in Neuroimmune Disorders.

    • Gerwyn Morris
    • Ken Walder
    • Basant K. Puri
    • Michael Berk
    • Michael Maes

    Oxidative and nitrosative stress (O&NS) is causatively implicated in the pathogenesis of Alzheimer’s and Parkinson’s disease, multiple sclerosis, chronic fatigue syndrome, schizophrenia and depression. Many of the consequences stemming from O&NS, including damage to proteins, lipids and DNA, are well known, whereas the effects of O&NS on lipoprotein-based cellular signalling involving palmitoylation and plasma membrane lipid rafts are less well documented. The aim of this narrative review is to discuss the mechanisms involved in lipid-based signalling, including palmitoylation, membrane/lipid raft (MLR) and n-3 polyunsaturated fatty acid (PUFA) functions, the effects of O&NS processes on these processes and their role in the abovementioned diseases. S-palmitoylation is a post-translational modification, which regulates protein trafficking and association with the plasma membrane, protein subcellular location and functions. Palmitoylation and MRLs play a key role in neuronal functions, including glutamatergic neurotransmission, and immune-inflammatory responses. Palmitoylation, MLRs and n-3 PUFAs are vulnerable to the corruptive effects of O&NS. Chronic O&NS inhibits palmitoylation and causes profound changes in lipid membrane composition, e.g. n-3 PUFA depletion, increased membrane permeability and reduced fluidity, which together lead to disorders in intracellular signal transduction, receptor dysfunction and increased neurotoxicity. Disruption of lipid-based signalling is a source of the neuroimmune disorders involved in the pathophysiology of the abovementioned diseases. n-3 PUFA supplementation is a rational therapeutic approach targeting disruptions in lipid-based signalling.

    This is available for free on Research Gate. Anyone know how people feel about posting stuff that is only available through Research Gate? I don't owe them dues; I just get access because I have a university email address through my employer. @Sushi ?

    -J
     
    Last edited: Sep 3, 2015
    joe12 and helen1 like this.
  2. Valentijn

    Valentijn Senior Member

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    Posting abstracts or short excerpts shouldn't be a problem in any event. Though the excerpts should be posted in the context of discussing them, rather than just reproducing large amounts of text/data.
     
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  3. JaimeS

    JaimeS Senior Member

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    Thanks, @Valentijn -

    So, having scanned this, it's a biochemical hypothesis that issues with fat metabolism due to NOS and ROS cause or contribute to a wide variety of the complains of ME/CFS and other neurologically-mediated disorders. The argument is logical and VERY well laid out. The 'suggestions for treatment' bit is tantalizing, but there's far more "here is my theory" than practical advice.

    The article ends by recommending CoQ-10 and ALA. Orly. Thanks.

    Still, I really feel like the framework of the argument is valuable in and of itself. :)

    -J
     
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  4. Valentijn

    Valentijn Senior Member

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    Yeah, been there and done that. Just like pretty much every other ME patient :rolleyes:
     
  5. JaimeS

    JaimeS Senior Member

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    There is a LOT more to this article than I initially stated. I'm still reading through, but it's actually kind of incredible. It's not a study; it's a review article, so it's summarizing everything, but it's talking about lipid oxidation in a way I haven't studied before. Maybe this will be a series of blog posts on my part because explanations are going to be pretty in-depth to explain.
     

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