Androgenetic Alopecia Pathway Update and Possible Cure

[beholder]

AnteUp, you never explicitly mentioned topical applying of PGE2 (drug dinoprostone) which can possibly still be obtained from gynaecologists and abortionists. PGE2 should be directly related to hair growth, in a good way.
Also you didn't mention bimatoprost (Lumigan/Latisse) which is chemically analogous to PGF2α and quite available (albeit a bit expensive). This one has been tested by babes all over the world and DOES grow hair/eyelashes. This will be the next thing I will be applying to scalp/temples to see if it strengthens existing hair and/or regrows "lost" hair.

Also, from what I have read the PGD2 (also PGE2) can be made by cells/body from both COX1 and COX2 which means we need aspirin or other NSAIDs to halt its production (I already do 250mg daily and it did result in stopping of shedding). PGE2 - which is also lost this way - can be replaced synthetically, possibly by a topical solution. Before anyone comments why people on aspirin don't grow hair: well this is why. We need to stop PGD2 and let other prostaglandins (PGE2, PGF2a) do the work instead.

As for minoxidil, besides what you wrote, it works by promoting systemic vascular relaxation and dilation in order to increase vascular circulation and blood flow to hair follicles and hair bulbs. Actually it just releases NO that activates the enzyme guanylate cyclase (sGC) which then causes the synthesis of the smooth muscle relaxant guanosine 3′,5′-monophosphate (cGMP). However, as soon as cGMP is produced another enzyme called phosphodiesterase 5 (PDE5) tends to degrade it and eliminate it. Further, and perhaps most significantly, after approximately 30 months of continuous use minoxidil shows a sharp drop in effectiveness probably due to local abundance of PDE5 which tends to fight the synthesis of cGMP which is needed as a vasodilator to enhance blood flow and vascular circulation. Thus we need not only nitrovasodilators like minoxidil or even nitroglycerin but also a cyclic guanosine 3′,5′-monophosphate (cGMP) specific PDE5 inhibitors such as sildenafil (\/iagra). Which is readily available as well. I already do apply sildenafil to scalp, btw.

 

[Fbalding84]

Great things we are discussing here guys!

And I agree with some of the things BEHOLDER has mentioned. I have experimenting with a very odd ingredient and like I have mentioned it's showing some results or I'm just going crazy and seeing this.

The solution will be a mixtures of ingredients not just one!!!! Bimatoprost might be expensive but I'm sure latanoprost is a lot cheaper and there have been studies on it potential.

Two things that might be off topic:
1. Every since I'm almost bald on certain areas the flaking, acne like bumps and itching has completely stopped. Is that a common thing? If so then this leads to only wonder that there might be some autoimmune response like AA.
2. When we let's say plug out a hair with tweezers. Does the hair bulge/ DP have a presence of stems cells that might beneficial to be used for let's say culturing the stems cells to reinjected like dr jahoda to grow a foreign hair (from the spouse) on Dr's own hair

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Also, from what I have read the PGD2 (also PGE2) can be made by cells/body from both COX1 and COX2 which means we need aspirin or other NSAIDs to halt its production
[/URL], btw.

We need one of those and asprin inhibits both. Oth while I have read minoxidil does it to only one of the COX1/2

 

[beholder]

We need one of those and asprin inhibits both. Oth while I have read minoxidil does it to only one of the COX1/2

Well, actually, COX-2 deletion in mice revealed that niacin evoked platelet COX-1–derived PGD2 biosynthesis. PGD2 appears to derive in roughly equal amounts from COX-1 and COX-2 in liver macrophages in vitro under basal and LPS-stimulated conditions, whereas in mast cells, PGD2 is initially derived from secretory phospholipase A2 (PLA2) and COX-1, followed by sustained formation by cytoplasmic PLA2 and COX-2. Source here: http://www.jci.org/articles/view/59262
So I think both COX-1 and COX-2 could be responsible for PGD2. And if we can block this biosynthesis and then add exogennous PGE2 and PGF2a then we'd be in clear I think.
Additionally, it would be nice to use Laropiprant to block the DP1 receptor which is stimulated by PGD2. Sadly the chemical seems to be found only coupled with niacin which greatly enhances PGD2 and PGE2 synthesis and is contrary to what we might want. Also it seems to be discontinued in EU, please correct me if I am wrong. It's pretty much can't-get-it here.

 

[Fbalding84]

I'm working with a compounding pharmacy and they can't get me almost and ingredient mixture I like. Anyone that wants to give me advise pls send me a PM

 

[hellouser]

I'm working with a compounding pharmacy and they can't get me almost and ingredient mixture I like. Anyone that wants to give me advise pls send me a PM

Check your private messages.

 

[minoxiDjunkie]

Sooo...
how do i get to apply lithium on my scalp/hair ???

 

[abcdefg]

When you guys figure out the cure can you let me know what it is? Heck if you figure out how to stop male pattern baldness from getting worse in this thread just let me know that. Just shoot me an email when this male pattern baldness thing is cured

 

[Take It Parise]

Minoxidil from what I described above causes inflammation, exacerbates andogenetic alopecia (Increase various PGs), but has its own unique pathway to grow hair; which is why hairs become minoxidil dependent.

So does that mean Finasteride/Dutasteride DON'T have a synergistic effect with Minoxidil? Or is Minoxidil-grown hair still affected by DHT?

 

[AnteUp]

So does that mean Finasteride/Dutasteride DON'T have a synergistic effect with Minoxidil? Or is Minoxidil-grown hair still affected by DHT?

It does have a synergistic effect. You are decreasing the conversion of androgens to DHT and using Minoxidil for its regrowth properties. Minoxidil grown hair can be affected by androgens if those androgens are not blocked.

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Atraric Acid a Potent Topical Antiandrogen:



I have known about Atraric Acid for many years. I learned about it because it is found in Pygeum bark, which many men use for BPH. I read about Atraric Acid a while back and no one seems to be that interested in it. This could be due to the fact that it comes from a natural source. However, Ataric Acid is a potent androgen receptor antagonist and has a high affinity for the androgen receptor. It binds to it and even prevents the translocation, meaning no matter what the androgen receptor will not produce a reaction. Not many antiandrogens can do this. This also applies to even mutated androgen receptors. NBBS is also an antiandrogen from pygeum, but I am more interested in Atraric Acid. If you do a simple search online, there are various articles stating that it is an antiandrogen, prevents nuclear translocation of the androgen receptor, agonist of estrogen receptors, and even a possible cure for prostate cancer.


Brevilin A the Natural JAK STAT Inhibitor:

Brevilin A is a natural JAK STAT Inhibitor found in a few plants. JAK STAT inhibitors are important. They inhibit the cascade which leads to hair loss caused by an upregulation of IL-6. Brevilin A works via STAT3, STAT1, and Janus Kinase 1 inhibition. Janus Kinase 1 is needed to create STAT6. IL4 inhibits preadipocytes and platelet derived growth factors via STAT6. I have been using Litsea Glutinosa topically it has been a good adjunct to my hair loss treatment. I have noticed some regrowth and thickening of vellus hairs. This may be due to the fact that it contains anti-inflammatory and wound healing abilities. What I find most important is that it contains Brevilin A. Unfortunatley, in a herbal extract we do not know how much Brevilin A is in the solution. I found out that in china there is a patent on it, but here in the US there cannot be a patent on natural compounds. It would be nice to find a reliable source for Brevilin A.

Trigonelline a PGD2 and Proteasome Inhibitor:

Trigonelline is found in nature. It is found in a few food items, one in particular is Fenugreek also known as Methi. I personally used a topical Fenugreek paste mixed with aloe vera for 3 moths a few years ago. At that time I did not know about Trigonelline. I used it because it was a time tested remedy used in south east asia. When I did use it, I did see some noticeable growth and thickening. Unfortunately, I stopped using it due to the fact that it was messy and time consuming to use.

Trigonelline has some important properties that are involved with hair loss. First of all it is a NRF2 inhibitor. NRF2 is the gene factor that creates Lipocalin PGD2 synthase which makes PGD2. Also, it has been shown, in a study regarding the pancreas, that it inhibits the proteasomal genes due to NRF2 inhibition. This means that it is a proteasome inhibitor. It also inhibits PPAR GAMMA(take a look below at Adipose and hair)

The ubiquitin proteasome pathway is responsible for tagging the cytoskeleton and for protease activation and degradation. This causes atrophy. So, if the proteasomal genes are inhibited then there is no tag for degradation via protease. Trigonelline acts as an indirect protease inhibitor, by inhibiting proteasome gene activation.

If Trigonelline is used topically, it should inhibit PGD2 and proteasome. This should mean we can possibly regrow miniaturized hairs. We need to find a supplier for this.



Arrector Pili muscle:

In androgenetic alopecia there is inflammation from the dermal papilla up to the bulge area causing thinning and miniaturization where the hair follicle keeps getting pushed up towards the scalp. In aloepcia areata there is only inflammation around the dermal papilla region, causing a stop in hair growth but the bulge remains untouched. The bulge cells create specific cells for the creation of the arrector pilli muscle seen here: http://www.cdb.riken.jp/tme/

The fact that we lose the arrector pilli muscle means that we lose a possible way for hairs in a follicular unit to "communicate." The loss of the AP muscle is also related to dysfunction of the bulge area which is responsible for the CD200 cells. Remember that CD200 and CD34 are lacking in androgenetic alopecia.

Adipose and hair:

Corticosteroids cause adipogenesis (decrease in preadipocytes) and also is anti-angiogenic (decrease vegf, etc). Corticosteroids are linked to insulin resistance, that is why I mentioned insulin resistance and IL-6, TNF alpha. Insulin resistance in fat cells cause an increase in IL-6 and TNF alpha. An increase in beta catenin, via inhibitor of GSk3, should inhibit PPAR Gamma. PPAR GAMMA causes adipogenesis. We need pre-adipocytes for hair regrowth/anagen.

IL-4 inhibits platelet derived growth factor (PDGH) via STAT6. PDGH is from preadipocytes (also in PRP).

I am not going to post links. If you want to check these facts over or get more information you can use PubMed and Google.

 

[Fbalding84]

Great finds Anteup.

Now Let's work on a list of ingredients and start producing our own topicals. I'm in to trial and I'm sure other are also.

 

[AnteUp]

Oxidants cause oxidative stress. Now that is clear, I want to explain why oxidants can regrow hair. There are two primary reasons why oxidants can regrow hair:

1) Oxidants can decrease proteasome degradation. Therefore, it can act a Proteasome inhibitor. Remember that people in the past have used Proteasome inhibitors topically and grew hair.

2) Oxidants can inhibit p16 senescence. P16 activation is directly involved with the balding dermal papilla. This means that if you inhibit p16 the balding process will stop with the possibility of regrowth.


Oxidants cause oxidative stress. Therefore they can cause damage. If you do not know what oxidative stress is, please read about it. Using them may be more harmful than good if you do not know how to use an oxidant properly for hair loss.


I urge all of you to do some research for yourself. Do a searches with oxidative stress and proteasome and another search with oxidative stress and p16. Use google, google scholar, and PubMed.


The key for oxidants to work is dose and time (cycling). This needs to be experimented with.


There are two oxidants that have been discussed with no explanation as to why they can work for hair loss. Now we know the scientific reason why oxidants can cause hair to regrow. Those oxidants were:


1) Chlorine Dioxide

2) Miconazole Nitrate (nitrates cause oxidative stress)


Hope this helps.

 

[minoxiDjunkie]

Oxidants cause oxidative stress. Now that is clear, I want to explain why oxidants can regrow hair. There are two primary reasons why oxidants can regrow hair:

1) Oxidants can decrease proteasome degradation. Therefore, it can act a Proteasome inhibitor. Remember that people in the past have used Proteasome inhibitors topically and grew hair.

2) Oxidants can inhibit p16 senescence. P16 activation is directly involved with the balding dermal papilla. This means that if you inhibit p16 the balding process will stop with the possibility of regrowth.


Oxidants cause oxidative stress. Therefore they can cause damage. If you do not know what oxidative stress is, please read about it. Using them may be more harmful than good if you do not know how to use an oxidant properly for hair loss.


I urge all of you to do some research for yourself. Do a searches with oxidative stress and proteasome and another search with oxidative stress and p16. Use google, google scholar, and PubMed.


The key for oxidants to work is dose and time (cycling). This needs to be experimented with.


There are two oxidants that have been discussed with no explanation as to why they can work for hair loss. Now we know the scientific reason why oxidants can cause hair to regrow. Those oxidants were:


1) Chlorine Dioxide

2) Miconazole Nitrate (nitrates cause oxidative stress)


Hope this helps.

i thought oxidants and oxidiation in the body is bad,
thats why they say that the antioxidants in fruits in vegs are good,
isnt it ?

 

[beholder]

Minoxidil and other vasodilators are radical NO (nitric oxide) donors as well. What is interesting is that NO is described as "modulating hair cycle" without any other specification. Interesting article here http://www.nature.com/jidsp/journal/v10/n3/full/5640220a.html

 

[beholder]

WTF?

Treat hair loss by trying to induce skin cancer?

Since when does tretinoin cause cancer anyway?

No worries, actually treating acute promyelocytic leukemia with tretinoin was a major breakthrough in APL therapy. Tretinoin is only teratogenous (causes developmental problems in fetus) and actually causes only apoptosis of sebaceous cells. http://www.ncbi.nlm.nih.gov/pubmed/16575387

But I do agree with general point that we need to rape follicles (with chemicals) by inducing their almost cancer-like growth. If we ever want to conquer this alopecia problem.

 

[Python]

No worries, actually treating acute promyelocytic leukemia with tretinoin was a major breakthrough in APL therapy. Tretinoin is only teratogenous (causes developmental problems in fetus) and actually causes only apoptosis of sebaceous cells. http://www.ncbi.nlm.nih.gov/pubmed/16575387

But I do agree with general point that we need to rape follicles (with chemicals) by inducing their almost cancer-like growth. If we ever want to conquer this alopecia problem.

currently with your finds, what are you on at the moment or what is your regimine. Or do you just stated what may work and seeking lab rats?

 

[AnteUp]

That was a mistake I made. Tretinoin helps treat cancer, so since our hair is being treated like a cancer, tretinoin which prevents cancer should help. It was a general comment I was trying to make so people would understand why it should work for hair growth.

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The pros and cons of ROS (reactive oxygen species), STAT3, HIF1

ROS:
Pro: Normal levels allow for angiogenesis. This is true for the mitochondria.
Cons:ROS created by mast cells is a problem we face in Androgenetic Alopecia. An up regulation in mitochondria causes apoptosis

Studies say ROS can cause or inhibit apoptosis-sometimes no clear answer, but the above statements are true. The problem is what is causing ROS and the environment(apoptosis or angiogenesis)

Stat3:
Pro: Stat 3 and Hif 1 alpha allows for VEGF production.

Cons:The problems is that STAT 3 is also involed with IL6 which is upregulated in Androgenetic Alopecia causing apoptosis. Also, STAT3 downregulates mitochondrial gene production, so it decreases its activity.

HIF1
CON:HIF causes a downregulation of the mitochondria to produce ROS

PRO:HIF1 is involved with angiogenesis

What I have noticed is that there is a cycle and particular environment which affects whether STAT3, ROS, HIF1 will cause apoptosis or angiogenesis. From what I noticed is some studies is that wounding causes angiogenesis in a time dependent manner expression involving ROS and HIF 1. I have said before, that cycling topicals to promote the hair follicle differentiation, proliferation, and eventual regrowth is something we need to really look into.


Quick addition: HIF 1 alpha is in the cytoplasm of cells and HIF 1 beta in the nucleus. When they both combine they can cause angiogenesis. HIF 1 alpha in the cytosol under normal oxygen conditions is degraded by the ubiquitin proteasome pathway. This is why a proteasome inhibitor is important for hair growth. To allow angiogenesis (hair growth) under normal oxygen conditions in our scalp.

NRF2 expression of antioxidants causes overexpression of the ubiquitin proteasome pathway-Another reason why it is important to inhibit NRF2


My question: What is the mechanism or pathway in which Neogenic (stemoxydine) works?

 

[frenchy]

quick research find this ..
"Hypoxia signaling is mediated by HIF1, the a subunit of which is degraded in an oxygen-dependent manner through prolyl-4-hydroxylase (P4H)-mediated hydroxylation. A potent P4H competitive inhibitor, Stemoxydine, was tested for its ability to induce hypoxia-like signaling."
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3500072/

 

[beholder]

Understood. I wasn't trying to call you out or anything. I initially thought using "cause" instead of "treat" was an obvious typo but the way the explanation was worded after confused me. I use tretinoin occasionally to try and take down these massive creases across my forehead so it definitely grabbed my attention.

tretinoin helps you with wrinkles? Damn, one more reason to put it into my regime. I don't have wrinkles per se [my forehead mostly acts like on botox, i.e. no movement] but there is one specific fine line which I am vorried about, one muscle I don't control. Superficial, I know.. but I guess that's why we're all here.

 

[AnteUp]

I glanced over the Garza et al paper and I found out something interesting. Androgenetic Alopecia scalp has all the stem cells needed, but it is lacking only two progenitor cells: CD34 (aka CD34+) and CD200 (aka CD200hiTGA6hi). In an update to the thread I stated how wounding effects the hair follicle. When the scalp is wounded, Lhx2 is activated in the hair follicle. Lhx2 inhibits Lgr5 which regulates bulge and secondary germ stem cells. Inhibiting Lgr5 will keep hair in anagen by inhibiting stem cell activation.



Here is the problem. Lgr5 is a marker for activated bulge and secondary hair germ cells. In the Garza et al study, they state that Lgr5 is reduced in bald scalp. Lgr5 is directly correlated with CD200hiITGA6hi cells (the cd200 cells that balding hairs lack). This means that we need to express Lgr5 in order to potentially regain the CD200 cells ( specifically CD200hiTGA6hi) that are lacking in androgenetic alopecia. What is interesting is that Lgr5 is considered as a tumor suppressor gene (Wikipedia).


This should mean that while wounding may help keep your existing hair in anagen for a short duration (5-7 days) it is inhibiting Lgr5 which has been shown to be responsible for CD200 (CD200hiTGAGhi).



If you have been wounding your scalp on a weekly basis, you are only keeping your terminal hair and thinning hairs that are not vellus in the anagen phase. This may be your cure if you have not receded or lost much hair; but be aware that suppressing Lgr5 for a long time and stopping wounding may have terrible consequences for your hair. Not to mention that long term wounding may lead to cancer. Lgr5 and CD200 is needed to form thick, terminal hair. I may have found one way to induce Lgr5/CD200. It would be nice if some of you can do some research and find potential other ways to do so. There needs to be some more medical research done on this as well.



There are studies showing that low dose Reactive Oxygen Species (ROS/Oxidants) can cause JNK and Lgr5 activation. JNK and tcf4 (activated by wounding via Lhx2) work together in tumorgenesis. Remember I stated before that our hair follicles are being treated like a tumor/cancer and in order to get regrowth we need to promote tumor like pathways. This is starting to get interesting.


Now for an update on CD34. The reason why Garza et al paper states that CD34+ is lacking is because of the decrease of the wnt/canonical pathway in Androgenetic Alopecia. In the thread where I made my second post, I said that I had discovered that TCF7 is directly involved with CD34. This is now a fact. Also, another fact is that when TCF7 is downregulated, CD34+ turn into CD34- cells. In order for us to increase CD34+ cells in the hair follicle, we need to activated the wnt canonical pathway and/or inhibit GSK3 Beta. A link below proves that LITHIUM can upregulate the proper type of TCF7 that will allow CD34+ cells to proliferate.





People have used the following topically, often separately, with relative success: oxidants, lithium chloride, androgen receptor inhibitors, and wounding. Many have had some success with them, but no cure. The reason is because each one is lacking or inhibiting something critical for the regrowth of terminal hair. Here is where I believe we have a potential cure:

1. Androgen Receptor Inhibition--stop the Androgenetic Alopecia pathway/cascade (inflammation, senescence, etc)
2. Lithium Chloride--Induce the Wnt B-Catenin pathway and CD34+ progenitor cells
3. Wounding--Induce anagen. Angiogenesis. Break fibrotic plaque. SOX9, Lhrx2, tcf4 hair follicle progenitor stem cell production
4. Low dose ROS (oxidant like hydrogen peroxide)-- induce Lgr5/CD200/CD200hiTGA6hi

This is what all 4 of the above should do--Regrowth of thick terminal hair



Now the question is if we need to cycle these or can we use them together. I have tried my best to understand Androgenetic Alopecia, the hair cycle, and all the factors involved with hair loss. I try to understand most of the material I read, but I am no expert. This is where we need the medical research community to get involved.



Inhibiting androgen receptors will cause the cessation of the androgenetic alopecia pathway of miniaturization, inflammation, and apoptosis . This is not a cure in itself because there has been senescent damage done to the androgen sensitive hair follicles. There are two types of damage. One is thinning of the hair follicle, but still retains the ability to grow. The other is miniaturization into vellus hairs. We have learned that we contain all the stem cells needed to regrow hair, but lack 2 progenitor cells (CD34 and CD200). Both of these cells are involved with the hair follicle cycle. Cd34 is more involved with anagen and CD200 with the diameter of the hair. We now have the potential to induce the proliferation of CD34 via lithium and CD200 via low dose ROS (hydrogen peroxide). Lithium and wounding will promote anagen. Wounding the scalp will allow (please read the 3 page pdf I posted a link to below) the other progenitor/stem cells proliferation involved with the hair follicle. Wounding will allow us to break fibrotic plaques and during healing will allow angiogenesis (blood vessels, etc) to take place; so that we can have the optimal environment for thick terminal hair. The low dose ROS oxidant should counteract the inhibition of Lgr5/CD200 during wounding.



Not all my links are about the hair follicle. If you want more proof, do your own search. Better yet, start talking to potential medical researchers about this and see if they can verify it. I would like to see a future study regarding this idea. I believe if I can do a simple online search, reading articles, and finding information as what I wrote above, there can be a way to cure Androgenetic Alopecia. The sad truth is that there is no money involved in a cure; especially if it is as simple as what I posted above. The money is in hair transplants, synthetic medicines, topicals, and injections. If we were to fund our own research or if the medical community obliges to sincerely help, we can find a cure.



Links:
http://www.sciencedirect.com/science/article/pii/S0092867411007562 (download the 3 page pdf)
http://www.ncbi.nlm.nih.gov/pubmed/20654575
http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002565
http://jcs.biologists.org/content/114/23/4329.full.pdf
http://mcr.aacrjournals.org/content/7/8/1189.full
http://www.pubfacts.com/detail/2292...cell-proliferation-via-the-JNK-signaling-path
http://www.ncbi.nlm.nih.gov/pubmed/21206086
http://www.jci.org/articles/view/44478
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067271/

 

[Python]

I glanced over the Garza et al paper and I found out something interesting. Androgenetic Alopecia scalp has all the stem cells needed, but it is lacking only two progenitor cells: CD34 (aka CD34+) and CD200 (aka CD200hiTGA6hi). In an update to the thread I stated how wounding effects the hair follicle. When the scalp is wounded, Lhx2 is activated in the hair follicle. Lhx2 inhibits Lgr5 which regulates bulge and secondary germ stem cells. Inhibiting Lgr5 will keep hair in anagen by inhibiting stem cell activation.



Here is the problem. Lgr5 is a marker for activated bulge and secondary hair germ cells. In the Garza et al study, they state that Lgr5 is reduced in bald scalp. Lgr5 is directly correlated with CD200hiITGA6hi cells (the cd200 cells that balding hairs lack). This means that we need to express Lgr5 in order to potentially regain the CD200 cells ( specifically CD200hiTGA6hi) that are lacking in androgenetic alopecia. What is interesting is that Lgr5 is considered as a tumor suppressor gene (Wikipedia).


This should mean that while wounding may help keep your existing hair in anagen for a short duration (5-7 days) it is inhibiting Lgr5 which has been shown to be responsible for CD200 (CD200hiTGAGhi).



If you have been wounding your scalp on a weekly basis, you are only keeping your terminal hair and thinning hairs that are not vellus in the anagen phase. This may be your cure if you have not receded or lost much hair; but be aware that suppressing Lgr5 for a long time and stopping wounding may have terrible consequences for your hair. Not to mention that long term wounding may lead to cancer. Lgr5 and CD200 is needed to form thick, terminal hair. I may have found one way to induce Lgr5/CD200. It would be nice if some of you can do some research and find potential other ways to do so. There needs to be some more medical research done on this as well.



There are studies showing that low dose Reactive Oxygen Species (ROS/Oxidants) can cause JNK and Lgr5 activation. JNK and tcf4 (activated by wounding via Lhx2) work together in tumorgenesis. Remember I stated before that our hair follicles are being treated like a tumor/cancer and in order to get regrowth we need to promote tumor like pathways. This is starting to get interesting.


Now for an update on CD34. The reason why Garza et al paper states that CD34+ is lacking is because of the decrease of the wnt/canonical pathway in Androgenetic Alopecia. In the thread where I made my second post, I said that I had discovered that TCF7 is directly involved with CD34. This is now a fact. Also, another fact is that when TCF7 is downregulated, CD34+ turn into CD34- cells. In order for us to increase CD34+ cells in the hair follicle, we need to activated the wnt canonical pathway and/or inhibit GSK3 Beta. A link below proves that LITHIUM can upregulate the proper type of TCF7 that will allow CD34+ cells to proliferate.





People have used the following topically, often separately, with relative success: oxidants, lithium chloride, androgen receptor inhibitors, and wounding. Many have had some success with them, but no cure. The reason is because each one is lacking or inhibiting something critical for the regrowth of terminal hair. Here is where I believe we have a potential cure:

1. Androgen Receptor Inhibition--stop the Androgenetic Alopecia pathway/cascade (inflammation, senescence, etc)
2. Lithium Chloride--Induce the Wnt B-Catenin pathway and CD34+ progenitor cells
3. Wounding--Induce anagen. Angiogenesis. Break fibrotic plaque. SOX9, Lhrx2, tcf4 hair follicle progenitor stem cell production
4. Low dose ROS (oxidant like hydrogen peroxide)-- induce Lgr5/CD200/CD200hiTGA6hi

This is what all 4 of the above should do--Regrowth of thick terminal hair



Now the question is if we need to cycle these or can we use them together. I have tried my best to understand Androgenetic Alopecia, the hair cycle, and all the factors involved with hair loss. I try to understand most of the material I read, but I am no expert. This is where we need the medical research community to get involved.



Inhibiting androgen receptors will cause the cessation of the androgenetic alopecia pathway of miniaturization, inflammation, and apoptosis . This is not a cure in itself because there has been senescent damage done to the androgen sensitive hair follicles. There are two types of damage. One is thinning of the hair follicle, but still retains the ability to grow. The other is miniaturization into vellus hairs. We have learned that we contain all the stem cells needed to regrow hair, but lack 2 progenitor cells (CD34 and CD200). Both of these cells are involved with the hair follicle cycle. Cd34 is more involved with anagen and CD200 with the diameter of the hair. We now have the potential to induce the proliferation of CD34 via lithium and CD200 via low dose ROS (hydrogen peroxide). Lithium and wounding will promote anagen. Wounding the scalp will allow (please read the 3 page pdf I posted a link to below) the other progenitor/stem cells proliferation involved with the hair follicle. Wounding will allow us to break fibrotic plaques and during healing will allow angiogenesis (blood vessels, etc) to take place; so that we can have the optimal environment for thick terminal hair. The low dose ROS oxidant should counteract the inhibition of Lgr5/CD200 during wounding.



Not all my links are about the hair follicle. If you want more proof, do your own search. Better yet, start talking to potential medical researchers about this and see if they can verify it. I would like to see a future study regarding this idea. I believe if I can do a simple online search, reading articles, and finding information as what I wrote above, there can be a way to cure Androgenetic Alopecia. The sad truth is that there is no money involved in a cure; especially if it is as simple as what I posted above. The money is in hair transplants, synthetic medicines, topicals, and injections. If we were to fund our own research or if the medical community obliges to sincerely help, we can find a cure.



Links:
http://www.sciencedirect.com/science/article/pii/S0092867411007562 (download the 3 page pdf)
http://www.ncbi.nlm.nih.gov/pubmed/20654575
http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002565
http://jcs.biologists.org/content/114/23/4329.full.pdf
http://mcr.aacrjournals.org/content/7/8/1189.full
http://www.pubfacts.com/detail/2292...cell-proliferation-via-the-JNK-signaling-path
http://www.ncbi.nlm.nih.gov/pubmed/21206086
http://www.jci.org/articles/view/44478
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067271/

I don't think I can go back to wounding. It was incredibly painful and just ended up shedding even more.

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I glanced over the Garza et al paper and I found out something interesting. Androgenetic Alopecia scalp has all the stem cells needed, but it is lacking only two progenitor cells: CD34 (aka CD34+) and CD200 (aka CD200hiTGA6hi). In an update to the thread I stated how wounding effects the hair follicle. When the scalp is wounded, Lhx2 is activated in the hair follicle. Lhx2 inhibits Lgr5 which regulates bulge and secondary germ stem cells. Inhibiting Lgr5 will keep hair in anagen by inhibiting stem cell activation.



Here is the problem. Lgr5 is a marker for activated bulge and secondary hair germ cells. In the Garza et al study, they state that Lgr5 is reduced in bald scalp. Lgr5 is directly correlated with CD200hiITGA6hi cells (the cd200 cells that balding hairs lack). This means that we need to express Lgr5 in order to potentially regain the CD200 cells ( specifically CD200hiTGA6hi) that are lacking in androgenetic alopecia. What is interesting is that Lgr5 is considered as a tumor suppressor gene (Wikipedia).


This should mean that while wounding may help keep your existing hair in anagen for a short duration (5-7 days) it is inhibiting Lgr5 which has been shown to be responsible for CD200 (CD200hiTGAGhi).



If you have been wounding your scalp on a weekly basis, you are only keeping your terminal hair and thinning hairs that are not vellus in the anagen phase. This may be your cure if you have not receded or lost much hair; but be aware that suppressing Lgr5 for a long time and stopping wounding may have terrible consequences for your hair. Not to mention that long term wounding may lead to cancer. Lgr5 and CD200 is needed to form thick, terminal hair. I may have found one way to induce Lgr5/CD200. It would be nice if some of you can do some research and find potential other ways to do so. There needs to be some more medical research done on this as well.



There are studies showing that low dose Reactive Oxygen Species (ROS/Oxidants) can cause JNK and Lgr5 activation. JNK and tcf4 (activated by wounding via Lhx2) work together in tumorgenesis. Remember I stated before that our hair follicles are being treated like a tumor/cancer and in order to get regrowth we need to promote tumor like pathways. This is starting to get interesting.


Now for an update on CD34. The reason why Garza et al paper states that CD34+ is lacking is because of the decrease of the wnt/canonical pathway in Androgenetic Alopecia. In the thread where I made my second post, I said that I had discovered that TCF7 is directly involved with CD34. This is now a fact. Also, another fact is that when TCF7 is downregulated, CD34+ turn into CD34- cells. In order for us to increase CD34+ cells in the hair follicle, we need to activated the wnt canonical pathway and/or inhibit GSK3 Beta. A link below proves that LITHIUM can upregulate the proper type of TCF7 that will allow CD34+ cells to proliferate.





People have used the following topically, often separately, with relative success: oxidants, lithium chloride, androgen receptor inhibitors, and wounding. Many have had some success with them, but no cure. The reason is because each one is lacking or inhibiting something critical for the regrowth of terminal hair. Here is where I believe we have a potential cure:

1. Androgen Receptor Inhibition--stop the Androgenetic Alopecia pathway/cascade (inflammation, senescence, etc)
2. Lithium Chloride--Induce the Wnt B-Catenin pathway and CD34+ progenitor cells
3. Wounding--Induce anagen. Angiogenesis. Break fibrotic plaque. SOX9, Lhrx2, tcf4 hair follicle progenitor stem cell production
4. Low dose ROS (oxidant like hydrogen peroxide)-- induce Lgr5/CD200/CD200hiTGA6hi

This is what all 4 of the above should do--Regrowth of thick terminal hair



Now the question is if we need to cycle these or can we use them together. I have tried my best to understand Androgenetic Alopecia, the hair cycle, and all the factors involved with hair loss. I try to understand most of the material I read, but I am no expert. This is where we need the medical research community to get involved.



Inhibiting androgen receptors will cause the cessation of the androgenetic alopecia pathway of miniaturization, inflammation, and apoptosis . This is not a cure in itself because there has been senescent damage done to the androgen sensitive hair follicles. There are two types of damage. One is thinning of the hair follicle, but still retains the ability to grow. The other is miniaturization into vellus hairs. We have learned that we contain all the stem cells needed to regrow hair, but lack 2 progenitor cells (CD34 and CD200). Both of these cells are involved with the hair follicle cycle. Cd34 is more involved with anagen and CD200 with the diameter of the hair. We now have the potential to induce the proliferation of CD34 via lithium and CD200 via low dose ROS (hydrogen peroxide). Lithium and wounding will promote anagen. Wounding the scalp will allow (please read the 3 page pdf I posted a link to below) the other progenitor/stem cells proliferation involved with the hair follicle. Wounding will allow us to break fibrotic plaques and during healing will allow angiogenesis (blood vessels, etc) to take place; so that we can have the optimal environment for thick terminal hair. The low dose ROS oxidant should counteract the inhibition of Lgr5/CD200 during wounding.



Not all my links are about the hair follicle. If you want more proof, do your own search. Better yet, start talking to potential medical researchers about this and see if they can verify it. I would like to see a future study regarding this idea. I believe if I can do a simple online search, reading articles, and finding information as what I wrote above, there can be a way to cure Androgenetic Alopecia. The sad truth is that there is no money involved in a cure; especially if it is as simple as what I posted above. The money is in hair transplants, synthetic medicines, topicals, and injections. If we were to fund our own research or if the medical community obliges to sincerely help, we can find a cure.



Links:
http://www.sciencedirect.com/science/article/pii/S0092867411007562 (download the 3 page pdf)
http://www.ncbi.nlm.nih.gov/pubmed/20654575
http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002565
http://jcs.biologists.org/content/114/23/4329.full.pdf
http://mcr.aacrjournals.org/content/7/8/1189.full
http://www.pubfacts.com/detail/2292...cell-proliferation-via-the-JNK-signaling-path
http://www.ncbi.nlm.nih.gov/pubmed/21206086
http://www.jci.org/articles/view/44478
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067271/

I don't think I can go back to wounding. It was incredibly painful and just ended up shedding even more.