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From: Kevlar -- repost from last forum
Date: 6/21/2002
Time: 5:10:04 PM
Remote Name: 128.95.248.229
Okay here goes a new idea I had today dealing with Fuchs studies on Wnt signaling in the follicle. She showed that Wnt's, especially 10b play a large role in follicle formation. Wnt binds to a receptor called Frizzled. When it does it activates a protein called Disheveled (DSH), which then binds to an enzyme called Glycogen Synthase Kinase-3 (GSK3). DSH when bound to GSK3 inhibits the action of GSK3. This is important for hair loss because active GSK3 binds to catenin and marks it for destruction and as Fuchs has demonstrated b-catenin is a key protien involved in the differentiation of stem cells to follicle cells, inhibition of mitosis, and to new hair cells. So in short without wnt the cell will degrade all of the catenin it has before it can reach the nucleus and bind with LEF1 to allow for transcription of hair growth protiens. We do not know what the proteins are that are produced from this cycle but we know that the more catenin the better our hair grows. Unfortunately, Fuchs tested the application of extra b-catenin on mice and it caused tumors to grow. I have a slightly different approach to getting more catenin production and that is to competitively inhibit GSK3 with an inderubin molecule. Small amounts can be found in Qing Dai (Indigo naturalis), which could be a possible beginning although isolated indirubins would probably be better. I am going to sleep on this idea and post more tomorrow since I am really tired right now but if anyone has any thoughts on this plan of attack let me know.
"A well-studied example is Danggui Longhui Wan, a mixture of 11 herbal medicines traditionally utilized against certain types of leukemias. Only one of these ingredients, Qing Dai (Indigo naturalis), a dark blue powder originating from various indigo producing plants, was found to carry the antileukemic activity (6). Although it is mostly constituted of indigo, a minor constituent, indirubin, was identified as the active component by the Chinese Academy of Medicine (7-9)."
"…indirubins are very potent inhibitors (IC50 values in the 5-50 nM range) of glycogen synthase kinase-3 (GSK-3 ). This kinase is an essential element of the WNT signaling pathway (29). It is involved in multiple physiological processes, including cell cycle regulation by controlling the levels of cyclin D1 (30) and catenin (31)…"
(scroll down to wnt signaling) http://carbon.cudenver.edu/~bstith/othrsys.htm
(scroll down to molecular controls on hair production) http://www.hairtransplantation.com/advances.html
http://www.mpasmb-hamburg.mpg.de/mand-pdf/leclerc_etal_2001.pdf
for those without adobe acrobate reader http://216.239.51.100/search?q=cache:Wy50m7k-A5YC:www.mpasmb-hamburg.mpg.de/mand-pdf/leclerc_etal_2001.pdf+glycogen+synthase+kinase+3+GSK3+inhibition+drugs&hl=en&ie=UTF-8
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