1. Sign our petition calling on Cochrane to withdraw their review of Exercise Therapy for CFS here.
    Dismiss Notice
  2. Guest, the 'News in Brief' for the week beginning 18th March 2024 is here.
    Dismiss Notice
  3. Welcome! To read the Core Purpose and Values of our forum, click here.
    Dismiss Notice

mTOR activation, ATG13 inactivation and suppression of autophagy

Discussion in 'Possible causes and predisposing factor discussion' started by belbyr, May 3, 2023.

  1. belbyr

    belbyr Established Member (Voting Rights)

    Messages:
    99
    Last edited by a moderator: May 3, 2023
  2. Hutan

    Hutan Moderator Staff Member

    Messages:
    26,530
    Location:
    Aotearoa New Zealand
    Screen Shot 2023-05-04 at 5.47.45 am.png

    That diagram from the video shows the rationale for the use of the Sim501 compound, in their attempt to make a drug induced model of PEM, which is the thing I wasn't sure about from my first listen.

    When mTOR is inactivated, ATG13 participates in processes leading to autophagy.
    When mTOR is activated, ATG13 is phosphorylated and inactivated, leading to disturbances in autophagy.
    SIM50 is reported to activate mTOR. So the mouse model involves activating mTOR via this drug.

    With the effect of the drug wearing off in the mice after a month, the question then becomes 'what is activating mTOR, and why does it remain activated?'.

    I agree @belbyr, I'm happy that these researchers are working on this.

    I don't think it is said, but I think SIM501 might be simvastin, a statin.
    [deleted a bit that is an unnecessary diversion]
    Does anyone here know for sure what SIM501 is?
     
    Last edited: May 4, 2023
    alktipping likes this.
  3. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

    Messages:
    4,256
    Location:
    Aotearoa New Zealand
    I would assume SIM501 is a code-name where SIM is chosen for "Simmaron Research". I haven't listened yet but from the above it sounds as if mTOR activation leads to ATG13 phosphorylation and badness, so simvastatin as an mTOR inhibitor might produce the opposite result?
     
    Hutan and alktipping like this.
  4. belbyr

    belbyr Established Member (Voting Rights)

    Messages:
    99
    Hutan likes this.
  5. Hutan

    Hutan Moderator Staff Member

    Messages:
    26,530
    Location:
    Aotearoa New Zealand
    Ah yes, that makes sense, I got tangled up in finding a statin referred to as SIM10 and making leaps from there. There's this paper https://pubmed.ncbi.nlm.nih.gov/23817226/
    where the statin inhibits mTOR and increases autophagy. As you say, the opposite result from what these researchers did in trying to create a mouse model of PEM.

    Some of our members will be on statins, I wonder if they have noticed any benefits.
     
    Last edited: May 4, 2023
    alktipping likes this.
  6. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

    Messages:
    1,860
    Hutan likes this.
  7. Hutan

    Hutan Moderator Staff Member

    Messages:
    26,530
    Location:
    Aotearoa New Zealand
    Yes, we have a few threads on rapamycin e.g.
    Rapamune / Rapamycin/ mTOR
    Results reported by members are variable but don't seem to be of the 'this cured me' type. And there's quite a lot of downside - an immune-suppressor in a pandemic...
     
    alktipping likes this.
  8. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

    Messages:
    4,256
    Location:
    Aotearoa New Zealand
    From The Multifaceted Role of Nutrient Sensing and mTORC1 Signaling in Physiology and Aging (2021, Frontiers in Aging) —

     

Share This Page