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Study: New HairLoss Treatment Based On Stopping Protein Aggregation

Discussion in 'Hair & Nails' started by Soren, Dec 1, 2017.

  1. Soren

    Soren Member

    Interesting new study that shows that protein binding might be one of the main causes of hair loss. Anyone off the top of their head can think of supplements that would prevent protein aggregation. The one that jumps out in my mind is Lanosterol but not sure if it would be relevant in this case. Maybe @haidut has some thoughts?

    "scientists at Choi Kang-yeol of Yonsei University in Seoul discovered that when a certain protein, CXXC5, binds to another protein called “Dishevelled," the combination restricts hair growth and wound regeneration.

    In their study, published in the Journal of Investigative Dermatology, they showed that they could prevent CXXC5 from binding to Dishevelled by adding a specially devised biochemical agent that blocks CXXC5. Without the binding between CXXC5 and Dishevelled, mice did not lose their hair, and bald mice even grew it back."
    Korean scientists move forward to cure baldness

    "When CXXC5 binds with a protein called the Dishevelled protein, it prevents follicle development and hair regrowth. A new biomaterial developed by the team interferes with this binding process. It's called PTD-DBM, and when applied to the bare skin of bald mice for 28 days, new follicles developed."
    Scientists Have Developed a Baldness Treatment That Helps Grow New Follicles

    Link to study here: Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound-Induced Hair Neogenesis - ScienceDirect

    Also some information on what "dishevelled" proteins are;
    "Dishevelled (Dsh) is a family of proteins involved in canonical and non-canonical Wnt signalling pathways. Dsh is a cytoplasmic phosphoprotein that acts directly downstream of frizzled receptors.[1] It takes its name from its initial discovery in flies, where a mutation in the dishevelled gene was observed to cause improper orientation of body and wing hairs.[2] It is thought to interact with the novel protein, SPATS1, when regulating the Wnt Signalling pathway.[3]"
    Dishevelled - Wikipedia

    Side note: I am pretty sure when they say protein binding they mean aggregation unless there is some subtle difference I am unaware of that someone wants to correct me on.
  2. Thoushant

    Thoushant Member

    To my knowledge of the WNT/Beta-catenin pathway is as follows:

    Beta-catenin is in constant synthesis in the cells, When it accumulates enough, it moves to the nucleus, binds to the DNA and starts transcribing HAIR GROWTH/proliferation related genes.
    This can go out of hand, and cancer happens, so the body limits Beta-catenin by having a complex constantly phosphorylate Beta-catenin, and this marks it for degradation by ubiquination.
    The complex is made of several proteins, including GSK-3B

    Heres how WNT and Dishevelled and this new peptide promote Beta-catenin and therefore hair growth:

    WNT binds to its membrane receptor. This allows Dishevelled(Also bound to WNT receptor at the membrane) to bind and inactivate the complex mentioned above, so now Beta-catenin is not marked for degradation and can accumulate.
    CXXC5 is competing with the complex above for Dishevelled binding. If CXXC5 takes all places, then the complex is free to roam and mark B-cats for degradation ->No hair growth.

    It's same pathways as GSK-3b inhibitors like Valproic acid or LithiumChloride, so I'm a bit confused over why it would be more effective than those, but CXXC5 might just be overexpressed in balding, is my guess..?
    btw: CXXC5 is regulated by Estradiol-ERalpha, and its alternative names is "retinoid induceable nuclear factor" and is also regulated by BMP4
    EDIT: AFAIK AR and DHT also regulates this complex, GSK-3b comes to mind with AR..
    Estradiol-Estrogen Receptor α Mediates the Expression of the <i>CXXC5</i> Gene through the Estrogen Response Element-Dependent Signaling Pathway
    in line of lowering estrogen, but maybe an ERalpha antagonist can somehow have a slight effect smilair
  3. OP

    Soren Member

    Thanks for that thoushant very good breakdown. Seems like promoting Beta-Catenin for hair growth might not be the best thing given the over proliferation can lead to cancer. However if the stress is a temporary acute stressor rather than a chronic one perhaps it is a viable treatment.

    Very intersting how CXXC5 expression is connected to Estrogen. From what I have seen estrogen seems to play an important role with regards to MPB.
  4. Thoushant

    Thoushant Member

    I might have used the wrong reason for the complex.. :p It's just how Beta-catenin is regulated. Some proteins need a signal to be transcribed and built, here it is unusual because it needs a signal to stop degrading, and I just put a reason..
    I personally don't worry too much(ehhh) about this and cancer. WNT/B-cat is lowered in baldness. Even if CXXC5 is taken out of the pictures, the body still has lots of ways to inhibit B-cat if it sees fit, Dkk-1 is one example.

    btw DHT promotes DKK-1, which inhibits WNT, (not gsk3b as I said earlier).
    DKK-1 seems to prevent WNT from binding to its receptor.

    I actually think this pathway is way more important than first perceived. Under the microscope, in balding there is sebacous gland hyperplasia, so there is an increase in sebacous cell numbers. In mice lacking Beta-catenin the same picture presents: less hair follicles and sebacous gland hyperplasia. So even in lack of Beta-catenin we get cell proliferation, (K.R. Smith 2008) argues that WNT drives proginator cells to HF, and lack of to Sebacous gland
    sebacous gland is robbing us of hair cells, IMO
  5. OP

    Soren Member

    The sebacous gland hyperplasia is an argument I've never heard before. Very interesting, might explain that most people with hair loss also have very oily scalps. Also might give some credence to the argument that shampooing and defatting of the scalp causes the body to overproduce sebacous glands.
  6. Thoushant

    Thoushant Member

    Good points.
    Besides the oily scalp, the shine can be attributed to poor stratum corneum barrier function. "skin translucency" teenage skin allows light penetration to deeper tissue: glowing skin, no shine. Ageing skin reflects and shines.
    It happens due to ROS that changes the protein structure of stratum corneum. Poor barrier function(And men generally have poorer barrier function than women) allows pathogens to enter, and inflammation. So I think improving the shine is a big step in preventing the hair loss spiral. I've started using urea since someone recommended it here.

    On the shampooing: I see your point. Sebum is also part of the barrier function, so removing too much allows pathogens to penetrate.
    Sebacous glands are part of the immune system, based on articles I've read. This makes sense. So low grade infection in the area might release some cytokines that promote sebacous glands, but it's bad when some pathogens rely on the sebum to live.
    I think besides the immune system, the pathogens themselves might change the genetic expression, to promote more food.

    Another thing with removing the fat: P. Acnes have a lipid wall(I take it other bacteria can too) , this allows it to go unrecognized by the immune system, strip this wall off and inflammation happens.

    I think my take away is there is some symbiosis going on at the scalp, and we're just restarting the relationship and spiral if we attack too strongly, instead we should focus on calming the immune system and calming the pathogen. The HF is just an innocent bystander to the war..