Changing stroke rehab and research worldwide now.Time is Brain! trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.

Monday, December 2, 2024

Ketone Bodies Clear Damaged Proteins in the Brain

 I'm sure your competent doctor has had a protocol on ketones for over a decade!

  • ketones (6 posts to February 2013)
  • NO? So, you don't have a functioning stroke doctor, do you?

    Ketone Bodies Clear Damaged Proteins in the Brain

    Summary: Ketone bodies, known for their role in energy metabolism during fasting, have been shown to directly interact with damaged proteins in the brain, aiding their clearance through autophagy. Researchers discovered that the ketone body β-hydroxybutyrate alters the solubility of misfolded proteins, facilitating their removal and reducing pathological aggregation.

    Tests in mouse models of Alzheimer’s and aging confirmed these effects, with treated animals showing improvements in protein quality control and brain health. This breakthrough provides a new metabolic link to aging and neurodegeneration, offering a potential pathway for therapeutic applications.

    Key Facts

    • Ketone bodies directly bind to misfolded proteins, enhancing their clearance via autophagy.
    • Mice treated with ketone esters displayed reduced aggregation of insoluble brain proteins.
    • Similar metabolites tested showed effects equal to or better than β-hydroxybutyrate.

    Source: Buck Institute

    Ketone bodies, produced by the body to provide fuel during fasting, have roles in regulating cellular processes and aging mechanisms beyond energy production.

    Research at the Buck Institute shows that ketone bodies can best be understood as powerful signaling metabolites affecting brain function in aging and Alzheimer’s disease.

    A new study demonstrates that ketone bodies and similar metabolites have profound effects on the proteome and protein quality control in the brain.

    This shows a neuron.
    While acknowledging that other mechanisms like energy supply are also important to brain health, Newman calls the discovery new biology. Credit: Neuroscience News

    Publishing in Cell Chemical Biology, Buck Institute scientists, working in mouse models of Alzheimer’s disease and aging, and in the nematode C. elegans, reveal the ketone body β-hydroxybutyrate interacts directly with misfolded proteins, altering their solubility and structure so they can be cleared from the brain through the process of autophagy.

    Previous studies have shown that boosting ketone bodies through diet, exercise and supplementation can be good for brain health and cognition, both in rodents and humans.

    Senior author John Newman, MD, PhD, an assistant professor at the Buck, says many theorized that the ketone body-based improvements were caused by increased energy to the brain or a reduction in brain inflammation, with reported improvements in amyloid plaques in mouse models being an indirect by-product. 

    “Now we know that’s not the whole story,” he said.  “Ketone bodies interact with damaged and misfolded proteins directly, making them insoluble so they can be pulled from the cell and recycled.” 

    While acknowledging that other mechanisms like energy supply are also important to brain health, Newman calls the discovery new biology.

    “It’s a new link between metabolism in general, ketone bodies and aging,” he said.

    “Directly linking changes in a cell’s metabolic state to changes in the proteome is really exciting.”

    Noting that ketone bodies are easy to manipulate experimentally and therapeutically, Newman adds, “This might be a powerful avenue to assist with global clearing of damaged proteins.

    “We’re just scratching the surface as to how this might be applied to brain aging and neurodegenerative disease.” 

    In addition to testing the changing solubility and structure of proteins in test tubes, the project also involved feeding a ketone ester to mice to confirm that the test tube results were reproduced in the brain. In mice, the ketone ester treatment resulted in clearance rather than pathological aggregation of insoluble proteins.

    The work also highlights the power of the Buck’s collaborative environment.

    The Schilling lab generated detailed proteome-wide solubility maps from both the test tube and mouse experiments.

    To test if the solubility changes caused by ketone bodies helped improve models of pathological aggregation, the  Lithgow lab fed ketone bodies to tiny nematode worms that were genetically modified to express the human equivalent of amyloid beta, which causes amyloid plaques.

    “The amyloid beta affects muscles and paralyzes the worms,” says Sidharth Madhavan, a PhD candidate and lead author on the study.

    “Once they were treated with ketone bodies the animals recovered their ability to swim. It was really exciting to see such a dramatic impact in a whole animal.”  

    Madhavan is now pursuing whether ketone bodies and related metabolites have similar effects outside the brain, such as in the gut. A key next step will be to test this new protein quality control mechanism in people to help guide how best to apply it in therapies, he adds.

    Newman says the study highlights a new form of metabolic regulation of protein quality control.

    “This is not just about ketone bodies,” he said.

    “We tested similar metabolites in test tubes and a bunch of them had similar effects. In some cases, they performed better than β-hydroxybutyrate. It’s beautiful to imagine that changing metabolism results in this symphony of molecules cooperating together to improve brain function.”

    Funding: This work was supported by the National Institutes of Health (NIH R01AG067333, NIA T32AG052374, NIA T32 AG000266, NIH R01AG067333-02S1), a sponsored research agreement from BHB Therapeutics, University of Southern California Provost Fellowship Funding, the Larry L. Hillblom Foundation, and Buck Institute institutional funding.

    About this neuroscience research news

    Author: Kris Rebillot
    Source: Buck Institute
    Contact: Kris Rebillot – Buck Institute
    Image: The image is credited to Neuroscience News

    Original Research: Open access.
    B-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer’s disease brain” by John Newman et al. Cell Chemical Biology

    No comments:

    Post a Comment