Chemistry:PTD-DBM
Protein Transduction Domain-fused Dishevelled Binding Motif (PTD-DBM) is a man-made peptide which interacts with the mechanism of the hair loss linked endogenous protein, CXXC5, which is a negative feedback regulator of the Wnt/β-catenin pathway. Application of the peptide to bald laboratory mice resulted in new hair follicle growth.[1] PTD-DBM is a peptide activating the Wnt/β-catenin signaling pathway functioning via interference of the binding of CXXC5 to Dishevelled (Dvl), an upstream component of the Wnt/β-catenin pathway. By topical application, the PTD-DBM promotes the formation of new hair follicles and prevents hair loss. Combinatory treatment of PTD-DBM with valproic acid (VPA), the activator of Wnt/β-catenin pathway, further induce hair re-growth as well as wound-induced hair neogenesis (WIHN).[2][1] The increased expression of CXXC5 in the bald scalps and excellent effects of PTD-DBM on hair growth in mice raised hopes for the application of this peptide on hair growth in the clinic.
Discovery of PTD-DBM
Professor Kang-Yell Choi and his research team at Yonsei University in South Korea discovered a protein responsible for hair loss in the condition known as androgenetic alopecia. The responsible protein is called CXXC-type zinc finger protein 5 (CXXC5),[2] which acts as a negative regulator for the Wnt/β-catenin pathway, involved in hair regeneration and wound healing.[2][1] CXXC5 negatively regulates hair growth, and the researchers developed a new substance that promotes hair regeneration by controlling the function of CXXC5. When CXXC5 binds with the Dvl protein, which functions at the upstream of Wnt/β-catenin pathway, it suppresses hair regrowth and hair follicle neogenesis.[1] The observation of CXXC5 overexpression in the bald scalp by Professor Choi’s team led to the development of PTD-DBM, which interferes with the CXXC5-Dvl protein-protein interaction (PPI).[3][1] By topical application, PTD-DBM enhances hair regrowth as well as neogenesis.[1] The hair growth promoting effect of PTD-DBM is further enhanced when used in combination with a Wnt/β-catenin signaling activator such as VPA, which is generally used as a drug for bipolar disorder and activates the Wnt/β-catenin pathway by inhibition of GSK3β.[1] Currently, topical application of PTD-DBM or its combination with VPA has been used for treatment of hair loss.
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Lee, Soung-Hoon; Seo, Seol Hwa; Lee, Dong-Hwan; Pi, Long-Quan; Lee, Won-Soo; Choi, Kang-Yell (November 2017). "Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound-Induced Hair Neogenesis" (in en). Journal of Investigative Dermatology 137 (11): 2260–2269. doi:10.1016/j.jid.2017.04.038. PMID 28595998.
- ↑ 2.0 2.1 2.2 Lee, Soung-Hoon; Kim, Mi-Yeon; Kim, Hyun-Yi; Lee, Young-Mi; Kim, Heesu; Nam, Kyoung Ae; Roh, Mi Ryung; Min, Do Sik et al. (2015-06-29). "The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing" (in en). Journal of Experimental Medicine 212 (7): 1061–1080. doi:10.1084/jem.20141601. ISSN 1540-9538.
- ↑ Kim, Hyun‐Yi; Choi, Sehee; Yoon, Ji‐Hye; Lim, Hwan Jung; Lee, Hyuk; Choi, Jiwon; Ro, Eun Ji; Heo, Jung‐Nyoung et al. (April 2016). "Small molecule inhibitors of the Dishevelled‐ CXXC 5 interaction are new drug candidates for bone anabolic osteoporosis therapy" (in en). EMBO Molecular Medicine 8 (4): 375–387. doi:10.15252/emmm.201505714. ISSN 1757-4676.
External links
- "Korean Scientists Develop Potential Drug Candidate for Hair Loss" - Business Korea
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