Updated Research and Knowledge - Cutting Edge

[TheKingofFighters]

Im afraid it would'nt be enough. You're gonna have to purify your vomit and apply it daily.

Luckily, some researcher have already came up with something a long time ago.

http://www.google.com/patents/WO1990011075A1?cl=en

A decreased vascularity of the scalp is considered to be a contributing factor to baldness since a good vascular supply is required for healthy hair follicles. Topically administered monobutyrin should penetrate the skin of the scalp and enhance the vascularity of the area containing hair follicles. This would result in the arrest qf hair loss. Formulations of the compounds of the invention are prepared using generally known excipients and carriers according to methods known in the art, such as those set forth in Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, PA (latest edition). For topical administration, especially for superficial lesions, standard topical formulations are employed using, for example, 10 -4-1% solutions of the compounds of the invention, with or without added growth factor, such as FGF, PDGF or EDGF. The topical prepara- tions would be applied daily or 2-3 times per week to the affected area. The concentration of the solution or other formulation depends on the severity of the wound and the nature of the subject. Formulations can be in a variety of known forms such as ointments, salves, gels, sprays, creams and lotions. For bone and tissue* repair, local and depot administration is preferred, or administration by sub¬ cutaneous or localized implant. Slow release forms can be included in polymers such as Hydron (Langer, R. , et al., Nature (1976) 263:797-799) or Elvax 40P (DuPont) (Murray, J.B., et al., In Vitro (1983) _19_:743-747) . Other sustained release systems have been suggested by Hsieh, D.S.T., et al., J Pharm Sci (1983) 72:17-22.

The patent above was done submitted in 1990. 26 years later, latest research still collaborates with that old patent's findings:

Thanks Swooping:

J Invest Dermatol. 2016 Apr 6. pii: S0022-202X(16)31024-7. doi: 10.1016/j.jid.2016.03.032. [Epub ahead of print]
Differential expression between human dermal papilla cells from balding and non-balding scalps reveals new candidate genes for androgenetic alopecia.
Chew EG1, Tan JH1, Bahta AW2, Ho BS3, Liu X1, Lim TC4, Sia YY1, Bigliardi PL5, Heilmann S6, Wan AC4, Nöthen MM6, Philpott MP2, Hillmer AM7. <=== this guy is the researcher who discovered the PAX1/FOXA2 balding locus for AGA
Author information
Abstract
Androgenetic alopecia (AGA) is a common heritable and androgen-dependent hair loss condition in men. Twelve genetic risk loci are known to date but it is unclear which genes at these loci are relevant for AGA. Dermal papilla cells (DPC) located in the hair bulb are the main site of androgen activity in the hair follicle. Widely used monolayer-cultured primary DPC in hair-related studies often lack dermal papilla (DP) characteristics. In contrast, immortalised DPC have high resemblance to intact DP. We derived immortalised human DPC lines from balding (BAB) and non-balding (BAN) scalp. Both BAB and BAN retain high proportions of DP signature gene and versican protein expression. We performed expression analysis of BAB and BAN and annotated AGA risk loci with differentially-expressed genes. We found evidence for AR but not EDA2R as the candidate gene at the AGA risk locus on chromosome X. Further, our data suggest TWIST1 and SSPN to be the functionally relevant AGA genes at the 7p21.1 and 12p12.1 risk loci, respectively. Down-regulated genes in BAB compared to BAN were highly enriched for vasculature-related genes, suggesting that deficiency of DPC from balding scalps in fostering vascularisation around the hair follicle may contribute to the development of AGA.
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Why monobutyrin?

I've said that the possible cure is in our vomit- and that active ingredient is Butyric acid. Monobutyrin is a prodrug(of Butyric acid) and it contains 1 molecule of Butyric acid and 1 molecule of Glycerin. When it enters a cell, Butyric acid is separated from the compound. Butyric acid by itself has only a few mins of half life- and it's the reason why we cant use it .

The patent contains a rather easyily-produced vehicle and the biggest advantage is that it contains NO ethanol. Ethanol(metabolised to acetaldehyde) is what contributes to the pathology of AGA- as seen in:

http://www.google.com/patents/US20110021599 . ALDH1A1 and AOX1
(9th and 11th most upregulated gene in balding scalp when compared to non-balding scalp, Cotsareli's patent), amongst other genes as well.

Formulation B:

A monobutyrin gel composition is prepared from the following:

Ingredient Amount

Monobutyrin 0.1 g

Hydroxyethylcellulose 250H 2.0 g

Glycerine 15.0 g

Chlorhexidine gluconate 0.25 g

Water q.s. 100.0 g

Inbeforethecure, please tell me what you think of all these.

[Swooping]

Hunting the genes in male-pattern alopecia: how important are they, how close are we and what will they tell us? - http://onlinelibrary.wiley.com/doi/1...exd.12965/epdf

I have sent you a pm for the other study (which is more important to you probably).

[TheKingofFighters]

Hunting the genes in male-pattern alopecia: how important are they, how close are we and what will they tell us? - http://onlinelibrary.wiley.com/doi/1...exd.12965/epdf

I have sent you a pm for the other study (which is more important to you probably).

Atually, i've just got it(the 2016 study) via the deepweb. Im reading through it now and it is giving me a headache because the microarray genes they ahve seems to be the opposite of the 1s in Cotsareli's patent. I have. I have to rethink everything all over again and these will probably take a few days for me to digest and figure out a good solution. Anyway, 1 thing seems for sure- and that is balding hair follicles have a deficient vasculature system( vasculature development,
blood vessel development and blood vessel
morphogenesis ) serving them.

The good news is I probably do not have to stray far because the belief that upregulating angiogenesis is the key to regrowing hair has been in my direction all along(Minoxidil is under-performing in this area).

[Swooping]

Indeed, no doubt that a phenomenon of AGA is the lack of vascularization of the miniaturized hair follicles. BUT, one must also see that a healthy hair follicle in telogen clearly lacks vascularization in comparison to anagen. Yet, a healthy hair follicle which is sitting in telogen vascularizes itself tremendously and does this constantly between anagen, catagen and telogen. Jahoda describes this well in a study of him.

It's exactly the same with adipose tissue. So all in all it's like this

Healthy hair follicle telogen (non-AGA) - lack of vascularization, lack of adipose tissue.

Miniaturized hair follicle (AGA) - lack of vascularization, lack of adipose tissue.

Healthy hair follicle anagen (NON-AGA) - vascularized, increased adipose tissue.



Anyway, I have a question for you and it's based on the following observation;

A third factor is aging. In normal men, advancing age is accompanied by increase in the incidence and extent of baldness. In eunuchs who were castrated prepubertally and given androgenic treatment at a later date,
those who are in the second decade of life when treatment is begun tend to lose hair slowly over a period of years, as in most normal young men of their age. In contrast, the eunuch who reaches the sixth decade of life
before receiving androgenic treatment loses his hair within a few months of the beginning of treatment. Evidently the susceptibility to alopecia increases with age but is not expressed in the absence of inciting agents like androgens (Hamilton, 1942).

So, both groups of eunuchs are perfect NW 1's. You inject them with androgens for the first time in their life. The older group tends to bald extremely fast, way faster than the younger group. Why? What's your view on this.

[TheKingofFighters]

MANUS CRIP T
ACCEP TED
A
CCEPTED MANUSCRIPT
21
Table 2:
List of vasculature-related genes that are down-re
gulated in balding DPC (BAB) compared to
non-balding DPC (BAN)
Gene Name
Median fold change
Gene Name
Median fold change
1nM DHT
10nM DHT
1nM DHT
10nM DHT
ACTC1
2.628
2.532
GNA13
-
1.885
ADORA2A
1.924
1.752
GUCY1A3
1.832
1.846
ADRA1B
1.833
1.749
HEY1
2.046
2.402
ADRB2 <== ok it's official. Those who are familiar with Steroids will have an idea what this is. Bambuterol, Clenbuterol, Salmaterol, etc. They are also anti-asthmatic agents and they exert vasodilatory effects.
2.106
2.590
HIF1A
2.557
2.670
AGT
2.008
1.881
HIF1A
2.806
2.850
AGTR1
2.788
2.643
HIF1A
2.822
2.546
AGTR1
2.803
2.621
HMOX1
1.895
1.934
AMOT
1.851
1.910
HTATIP2
6.764
6.038
ANGPTL4
2.054
2.220
ITGA1
2.008
1.956
ANXA2
2.500
2.211
ITGA4
1.784
1.748
APOLD1
2.371
2.661
JUNB
2.325
2.002
BGN
2.314
2.324
KLF5
1.738
1.802
CAV1
2.884
2.708
LEPR
2.042
1.987
CAV2
1.857
1.954
LOX
3.116
2.974
CAV2
1.819
1.775
MMP14
2.090
2.003
CAV2
1.827
1.741
NOS3
2.154
1.955
CCBE1
2.250
2.171
NOTCH1
1.713
1.813
CDH13
1.829
1.867
P2RX4
1.830
1.806
CDH2
1.734
1.782
PDE5A
2.809
2.697
CHD7
2.047
2.187
PDPN
1.931
1.957
CITED2
2.967
2.623
PLAU
1.788
1.882
COL1A1
5.069
4.926
PLCD3
1.750
1.770
COL1A2
1.808
1.757
PLXDC1
1.992
1.846
COL3A1
3.723
3.615
PPAP2B
1.879
1.870
COL18A1
16.750
15.675
PPAP2B
2.235
2.225
CTGF
3.546
3.587
RECK
2.463
2.351
CTGF
3.963
4.229
RECK
2.458
2.314
CXCL12
2.635
2.631
SCG2
5.365
5.938
CXCL12
2.391
2.151
SGPL1
1.910
1.828
CXCL12
2.518
2.643
SMAD7
1.841
1.729
CYR61
3.167
3.023
SMO
1.783
1.830
DHCR7
23.464
20.353
SOD2
-
1.752
DHCR7
17.994
14.520
SOD2
2.306
2.355
DICER1
1.860
1.800
SOD2
1.969
2.367
DICER1
1.896
1.898
TGFA
3.281
3.060
EDNRA
1.831
1.978
TGFA
2.146
2.328
EREG
1.986
2.303
THY1
2.871
2.781
FGF2
2.087
2.018
TNFAIP2
3.180
2.792
FGF2
1.971
1.954
ZC3H12A
1.890
2.237
GCH1
2.957
3.348
ZFP36L1
3.244
3.055
GNA13
1.784
1.755
ZMIZ1
1.835
1.746

The good news here for those of Anglo-saxon descent:

MATERIALS AND METHODS
Isolation and immortalisation of human balding and
non-balding primary DPC
Between one and three DP were isolated from each ma
tched 2 mm punch biopsies of balding (frontal) and
non-balding (occipital) scalps of male AGA patients
who were undergoing hair transplant surgery and no
t
currently on hair loss medications, as described pr
eviously (Bahta
et al.
, 2008; Philpott
et al.
, 1994;
Upton
et al.
, 2015). Ethics approval was obtained from East Lon
don and City health authority (T/98/008)
and all biopsies were taken with full patient writt
en consent. All experiments adhered to the Declarat
ion
of Helsinki Principles. Isolated primary DPCs were
cultured up to passage 3 (
Supplementary Materials
and Methods
) and immortalised with hTERT using pBABEhygro-hTER
T. Hygromycin-resistant clones
with stable hTERT expression were then cultured as
described in the
Supplementary Materials and
Methods
. We were able to derive one immortalized balding (
BAB) and one non-balding (BAN) cell line
originating from two different male individuals due
to limitation in tissue materials, difficulties in
establishing pure primary DPC cultures and low tran
sformation efficiencies. Both BAB and BAN have
been established from Anglo-Saxon males with Hamilt
on scale 4 AGA.

That list above applies to these group of men.

[TheKingofFighters]

Indeed, no doubt that a phenomenon of AGA is the lack of vascularization of the miniaturized hair follicles. BUT, one must also see that a healthy hair follicle in telogen clearly lacks vascularization in comparison to anagen. Yet, a healthy hair follicle which is sitting in telogen vascularizes itself tremendously and does this constantly between anagen, catagen and telogen. Jahoda describes this well in a study of him.

It's exactly the same with adipose tissue. So all in all it's like this

Healthy hair follicle telogen (non-AGA) - lack of vascularization, lack of adipose tissue.

Miniaturized hair follicle (AGA) - lack of vascularization, lack of adipose tissue.

Healthy hair follicle anagen (NON-AGA) - vascularized, increased adipose tissue.



Anyway, I have a question for you and it's based on the following observation;



So, both groups of eunuchs are perfect NW 1's. You inject them with androgens for the first time in their life. The older group tends to bald extremely fast, way faster than the younger group. Why? What's your view on this.

I do not and wont be able to give any comments without any data or genes to examine

[InBeforeTheCure]

Looking forward to it. I can see we both have started from the same point, the genes it looks like. If indeed JAK/STAT inhibition does end up reversing AGA it would only make sense that the team that discovered the key pieces of information and cure to hair loss ( Christiano's team ) is a team that focuses on the genetics behind all types of hair loss.

I was looking more at gene expression data and major pathways, but I've been looking more at GWAS again lately too.

BTW, i greatly appreciate yours and mlamber5's valuable input into this topic(PAX1).

Well, thank you.

Inbeforethecure- Give me your valuable input on this:

http://www.wikipathways.org/index.php/Pathway:WP2840

Look at 'NR3C1'(centre/south of the diagram)- that's the Gluccocorticoid receptor and it's in a direct relationship with FOS(aka c-FOS) and FOSB

Then look at this http://www.google.com/patents/US20110021599 - Dr Cotsareli's patent on the most downregulated genes in non-balding scalp when compared to balding scalp. FOS and FOSB are the 3rd and 4th most downregulated genes in non-balding scalp, respectively.

What do you think? Gluccocorticoid underexpression or overexpression in AGA? Gluccocorticoid resistance?

According to the Chew/Philpott data, there's no difference in NR3C1 expression in balding vs. non-balding DPCs, while c-fos is downregulated in balding DPCs. Don't know about epithelial parts of the HF for NR3C1. But a lot of things can regulate c-fos and most other genes, so a computational approach is really best-suited for guessing at relationships among vast amounts of data.

As for the rest of it, I don't think I can keep up with you.

Also, a lot of these things I don't really know well enough to comment. I need to study the epithelial HF interactions a lot more, and I think when dealing with the complex details of this, computational approaches would be necessary. I will ask this about MSX2 though: Since MSX2 is a signature gene for matrix cells and transit amplifying cells, could it be that MSX2 is lower in balding scalp simply because the follicles are miniaturized?

FYI, in a recent study by Philpott et al. , they did not find any differences of PAX1 between balding DPC and non-balding. Interestingly, FOXA2 wasn't even expressed.

They didn't really detect PAX1 either beyond "background" levels. I would guess that it's only a transiently expressed gene, either embryonic or during a particular part of the hair cycle (early anagen is a good candidate for that).

At the susceptibility loci 7p21.1 (HDAC9 & TWIST1) they found only TWIST1 to be differentially expressed in balding DPC vs non-balding DPC (upregulated), not HDAC9.

Knockout of TWIST1 in a mice model (BLEGH) was found to dramatically enhance the anagen phase in a study. Also TWIST1 has shown to be able to upregulate AR by binding to E-boxes in the AR promoter.

Yes, the HDAC9 spot is probably a regulatory region for TWIST1.
Variants in an Hdac9 intronic enhancer plasmid impact Twist1 expression in vitro

@InBeforeTheCure,

Great man, keep it up. I have troubles understanding how you would be able to underline a strong hypothesis based on the current genetic data? I compare it to walking around in a very big complex labyrinth where one is drunk without a map. I might be wrong though. Very curious to your findings.

I wouldn't call it a "strong" hypothesis, because to me a strong hypothesis would need to have the following properties:

1) It must explain all or at least most aspects of what we know about AGA.
2) It must explain the role of most of the genes that show up in GWAS.
3) Obviously, it must give definite predictions that could in practice be falsifiable (otherwise, it's pseudoscience)

Then if many experiments are done that confirm the predictions of the hypothesis, it would be elevated to the status of a theory.

I would say that what I've got only partially provides 1) (it needs more development and refinement). It only partially matches 2) -- a couple of the major risk genes do have definite roles in the model, one of which I wasn't even aware was in the GWAS results until afterwards, and the others don't really have definite roles. PAX1 is known to interact with a key transcription factor of the model and change its binding sites, but I can't say what the nature of that change would be. Other genes I haven't investigated closely enough yet. It does provide 3), and should provide more predictions with further development.

I do think though that I'm going to post the most important things of what I've got so far right away, because I hate talking about it in vague terms.

The biggest problem in my opinion also resides with what you mention and that is the "experiment". We lack a proper model. We only have and use rodent models. Every researcher now finally is aware that it's a horrible model for AGA and we desperately need a proper one. Harsher regulations etc. made it impossible to test on a macaque model like in the past (correct decision imo, but that aside). So how are you going to be able to cope with this problem? Slap stuff on your scalp?

True. The best we have now is...what? Tissue samples with the hairs inside?

Speaking of SHH, the SHH agonist that was in development by Curis and Procter & Gamble back in 2005 for androgenetic alopecia had huge excitement, but didn't proceed to human clinical trial testing as it was touted to be to dangerous. After all AGA is seen as a cosmetic disease and not a life threatening one, which hugely added to their decision. That was a black point. That being said I'm still intrigued by the SHH pathway simply because a SHH antagonist induces alopecia in approximately 70% of subjects as a side effects from the top of my head, which might even be very long lasting after discontinuation (longer than a year). Based on this observation alone one could at least argue that the pathway seems to have a huge role in hair follicle function.

Yes, definitely. The Shh pathway is known to have a huge role in hair follicle function. I don't think Shh agonists would do anything miraculous for AGA though.

Anyway, I have a question for you and it's based on the following observation;



So, both groups of eunuchs are perfect NW 1's. You inject them with androgens for the first time in their life. The older group tends to bald extremely fast, way faster than the younger group. Why? What's your view on this.

I have a question. Do you know if when those older eunuchs are injected with androgens, do they also show accelerated facial hair growth? If so, it would hint that AGA is a programmed developmental event. If not, it's more likely that this phenomenon could be the result of increased sensitivity of DPCs to stress with increasing age.

Also, the data for the Chew/Philpott paper are available on GEO. It's GSE66663 and GSE66664.

[InBeforeTheCure]

Also, the data for the Chew/Philpott paper are available on GEO. It's GSE66663 and GSE66664.

I've also filtered the data for those transcripts strongly detected in balding DPCs or non-balding DPCs or both, and calculated the fold change between the average of the balding samples and the average of the non-balding samples for each gene. I've uploaded that here: https://www.dropbox.com/s/k8t4aaa6en..._data.csv?dl=0

I also ran a quick pathway analysis for the top 1,000 upregulated genes in balding DPCs with DAVID:



...and for the top 1,000 downregulated genes:

[karxxx]

my opinion .
DHT resistant hair makes it very difficult.
Beard stem cells is the solution.
beard stem cells transplants are one solution.

[TheKingofFighters]

I've also filtered the data for those transcripts strongly detected in balding DPCs or non-balding DPCs or both, and calculated the fold change between the average of the balding samples and the average of the non-balding samples for each gene. I've uploaded that here: https://www.dropbox.com/s/k8t4aaa6en..._data.csv?dl=0

I also ran a quick pathway analysis for the top 1,000 upregulated genes in balding DPCs with DAVID:



...and for the top 1,000 downregulated genes:

7 68,611,960 rs69455416 7q11.22 []---AUTS2 AUTS2 down - - - - 2.801 2.868

AUTS2 is a gene downregulated in BAB(balding scalp. So we need to upregulate it)

read this:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4468360/

Possible functional links among brain- and skull-related genes selected in modern humans

The sequencing of the genomes from extinct hominins has revealed that changes in some brain-related genes have been selected after the split between anatomically-modern humans and Neanderthals/Denisovans. To date, no coherent view of these changes has been provided. Following a line of research we initiated in Boeckx and Benítez-Burraco (2014a), we hypothesize functional links among most of these genes and their products, based on the existing literature for each of the gene discussed. The genes we focus on are found mutated in different cognitive disorders affecting modern populations and their products are involved in skull and brain morphology, and neural connectivity. If our hypothesis turns out to be on the right track, it means that the changes affecting most of these proteins resulted in a more globular brain and ultimately brought about modern cognition, with its characteristic generativity and capacity to form and exploit cross-modular concepts, properties most clearly manifested in language.

Keywords: language-ready brain, skull morphology, human evolution, Neanderthals/Denisovans, anatomically modern humans, AUTS2, FOXP2, RUNX2

[TheKingofFighters]

7 68,611,960 rs69455416 7q11.22 []---AUTS2 AUTS2 down - - - - 2.801 2.868

AUTS2 is a gene downregulated in BAB(balding scalp. So we need to upregulate it)

read this:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4468360/

Possible functional links among brain- and skull-related genes selected in modern humans

The sequencing of the genomes from extinct hominins has revealed that changes in some brain-related genes have been selected after the split between anatomically-modern humans and Neanderthals/Denisovans. To date, no coherent view of these changes has been provided. Following a line of research we initiated in Boeckx and Benítez-Burraco (2014a), we hypothesize functional links among most of these genes and their products, based on the existing literature for each of the gene discussed. The genes we focus on are found mutated in different cognitive disorders affecting modern populations and their products are involved in skull and brain morphology, and neural connectivity. If our hypothesis turns out to be on the right track, it means that the changes affecting most of these proteins resulted in a more globular brain and ultimately brought about modern cognition, with its characteristic generativity and capacity to form and exploit cross-modular concepts, properties most clearly manifested in language.

Keywords: language-ready brain, skull morphology, human evolution, Neanderthals/Denisovans, anatomically modern humans, AUTS2, FOXP2, RUNX2

This means our skull shape has got something to do with AGA. This fits in with the 'skull expansion theory'.

[burtandernie]

"So, both groups of eunuchs are perfect NW 1's. You inject them with androgens for the first time in their life. The older group tends to bald extremely fast, way faster than the younger group. Why?

Doesnt this though perfectly explain why in most men as they get older fin seems to stop working? There rate of sensitivity increases as they get older, and the androgens left over are enough to continue the balding process. It also explains why men as they age even when androgen levels naturally decline actually keep balding sometimes it even speeds up. Of course why is hair sensitive to begin with is the million dollar question, and the answer is probably pretty complicated.

[TheKingofFighters]

1)MAPT is 1 of the root causative AGA gene downregulated in balding scalp=> need to UP(Estradiol)
2)SSPN is 1 of the root causative AGA gene downregulated in balding scalp => need to UP(PPAR Alpha)
3)AUTS2 is 1 of the root causative AGA gene downregulated in balding scalp => need to UP(PPAR Alpha)
4)TWIST1 is 1 of the root causative AGA gene upregulated in balding scalp => need to DOWN(Estradiol)
5)RNF145 is 1 of the root causative AGA gene downregulated in balding scalp => need to UP(Phenobarbital)
6)TWIST2 is 1 of the causative AGA gene downregulated in balding scalp => need to UP(Estradiol)
7)PER2 is 1 of the causative AGA gene downregulated in balding scalp => need to UP(Estradiol)

8)UBIAD1 is 1 of the causative AGA gene upregulated in balding scalp => need to DOWN(Dibutyl Phthalate, Caffeine)
9)SRM is 1 of the causative AGA gene upregulated in balding scalp => Need to DOWN(Estradiol) <=== this gene stands for 'Spermidine synthase'. seems like those that carry the AGA variant of this gene has too much of Spermidine production in the balding scalp:

At the 1p36 locus, non-differentially-expressed candidate gene TARDBP (TAR DNA binding protein) is
unlikely to be causative. Instead, SRM, previously mentioned as a potential candidate gene due to its
proximity to rs12565727 (Li et al., 2012), was up-regulated in BAB(balding scalp) compared to BAN. SRM is involved
in the synthesis of spermidine which acts on matrix keratinocytes to promote hair elongation and prolong
anagen (Ramot et al., 2011). However, the effect of SRM activity and the resultant spermidine
synthesized in DPC is unknown. Further, we found CASZ1, EXOSC10, FRAP1, and UBIAD1 to be
differentially-expressed at this locus. They provide new potential candidate genes for hair loss/growth
modulation.

10)FRAP1 is 1 of the causative AGA gene upregulated in balding scalp => Need to DOWN(?)
11)EXOSC10 => is 1 of the causative AGA gene upregulated in balding scalp => need to DOWN(Dibutyl Phthalate)
12)CASZ1 is 1 of the causative AGA gene downregulated in balding scalp => need to UP(PPAR ALpha, Butyraldehyde)
13)AR is 1 of the causative gene upregulated in balding scalp => need to DOWN(AR blockers) <== the AGA-variants of this gene are not present in East Asians.

Total = 17 AGA locus genes known so far. 4 of them were not differentially-regulated when exposed to DHT:

14)WNT10A
15)Between SUCNR1 and MBNL1
16)SETBP1
17)Between PAX1 and FOXA2. FOXA2's expression were not detected in balding scalp and PAX1's expression was not found to be differentially expressed when DPCs were exposed to DHT.


Seems like a PPAR Alpha agonist and Estradiol are what we need to regrow hair

[TheKingofFighters]

1)MAPT is 1 of the root causative AGA gene downregulated in balding scalp=> need to UP(Estradiol)
2)SSPN is 1 of the root causative AGA gene downregulated in balding scalp => need to UP(PPAR Alpha)
3)AUTS2 is 1 of the root causative AGA gene downregulated in balding scalp => need to UP(PPAR Alpha)
4)TWIST1 is 1 of the root causative AGA gene upregulated in balding scalp => need to DOWN(Estradiol)
5)RNF145 is 1 of the root causative AGA gene downregulated in balding scalp => need to UP(Phenobarbital)
6)TWIST2 is 1 of the causative AGA gene downregulated in balding scalp => need to UP(Estradiol)
7)PER2 is 1 of the causative AGA gene downregulated in balding scalp => need to UP(Estradiol)

8)UBIAD1 is 1 of the causative AGA gene upregulated in balding scalp => need to DOWN(Dibutyl Phthalate, Caffeine)
9)SRM is 1 of the causative AGA gene upregulated in balding scalp => Need to DOWN(Estradiol) <=== this gene stands for 'Spermidine synthase'. seems like those that carry the AGA variant of this gene has too much of Spermidine production in the balding scalp:

At the 1p36 locus, non-differentially-expressed candidate gene TARDBP (TAR DNA binding protein) is
unlikely to be causative. Instead, SRM, previously mentioned as a potential candidate gene due to its
proximity to rs12565727 (Li et al., 2012), was up-regulated in BAB(balding scalp) compared to BAN. SRM is involved
in the synthesis of spermidine which acts on matrix keratinocytes to promote hair elongation and prolong
anagen (Ramot et al., 2011). However, the effect of SRM activity and the resultant spermidine
synthesized in DPC is unknown. Further, we found CASZ1, EXOSC10, FRAP1, and UBIAD1 to be
differentially-expressed at this locus. They provide new potential candidate genes for hair loss/growth
modulation.

10)FRAP1 is 1 of the causative AGA gene upregulated in balding scalp => Need to DOWN(?)
11)EXOSC10 => is 1 of the causative AGA gene upregulated in balding scalp => need to DOWN(Dibutyl Phthalate)
12)CASZ1 is 1 of the causative AGA gene downregulated in balding scalp => need to UP(PPAR ALpha, Butyraldehyde)
13)AR is 1 of the causative gene upregulated in balding scalp => need to DOWN(AR blockers) <== the AGA-variants of this gene are not present in East Asians.

Total = 17 AGA locus genes known so far. 4 of them were not differentially-regulated when exposed to DHT:

14)WNT10A
15)Between SUCNR1 and MBNL1
16)SETBP1
17)Between PAX1 and FOXA2. FOXA2's expression were not detected in balding scalp and PAX1's expression was not found to be differentially expressed when DPCs were exposed to DHT.


Seems like a PPAR Alpha agonist and Estradiol are what we need to regrow hair

Furthermore, the identification of MAPT as the relevant AGA candidate gene at 17q21.31
instead of SPPL2C suggests that changes in MAPT function connect the risk for AGA with the risk for
Parkinson’s disease (Li et al., 2012).

Those who have a family history of Parkinson's could be a carrier of the AGA variant of MAPT.

[TheKingofFighters]

Furthermore, the identification of MAPT as the relevant AGA candidate gene at 17q21.31
instead of SPPL2C suggests that changes in MAPT function connect the risk for AGA with the risk for
Parkinson’s disease (Li et al., 2012).

Those who have a family history of Parkinson's could be a carrier of the AGA variant of MAPT.

4 of them were not differentially-regulated when exposed to DHT:

14)WNT10A
15)Between SUCNR1 and MBNL1
16)SETBP1
17)Between PAX1 and FOXA2. FOXA2's expression were not detected in balding scalp and PAX1's expression was not found to be differentially expressed when DPCs were exposed to DHT.

This could mean that these AGA-causing locus are androgen pathway-independent in the DPCs of the balding scalp.

In any case:

1)WNT10A = Estradiol(UP), Butyraldehyde =(UP)- assuming that WNT10A is downregulated in balding scalp

2a)SUCNR1, from genecards:

This gene encodes a G-protein-coupled receptor for succinate, an intermediate molecule of the citric acid cycle. It is involved in the promotion of hematopoietic progenitor cell development, and it has a potential role in renovascular hypertension which has known correlations to renal failure, diabetes and atherosclerosis. [provided by RefSeq, Oct 2009]

2b)MBNL1, from genecards:

This gene encodes a member of the muscleblind protein family which was initially described in Drosophila melanogaster. The encoded protein is a C3H-type zinc finger protein that modulates alternative splicing of pre-mRNAs. Muscleblind proteins bind specifically to expanded dsCUG RNA but not to normal size CUG repeats and may thereby play a role in the pathophysiology of myotonic dystrophy. Mice lacking this gene exhibited muscle abnormalities and cataracts. Several alternatively spliced transcript variants have been described but the full-length natures of only some have been determined. The different isoforms are thought to have different binding specificities and/or splicing activities. [provided by RefSeq, Sep 2015]

3)SETBP1, from genecards:

This gene encodes a protein which contains a several motifs including a ski homology region and a SET-binding region in addition to three nuclear localization signals. The encoded protein has been shown to bind the SET nuclear oncogene which is involved in DNA replication. Mutations in this gene are associated with Schinzel-Giedion midface retraction syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]


4)Pax1(Estradiol=UP, Butyraldehyde=UP), from genecards:

This gene is a member of the paired box (PAX) family of transcription factors. Members of the PAX family typically contain a paired box domain and a paired-type homeodomain. These genes play critical roles during fetal development. This gene plays a role in pattern formation during embryogenesis and may be essential for development of the vertebral column. This gene is silenced by methylation in ovarian and cervical cancers and may be a tumor suppressor gene. Mutations in this gene are also associated with vertebral malformations. [provided by RefSeq, Mar 2012]