Protein Transduction Domain-fused Dishevelled Binding Motif (PTD-DBM) is a man-made

peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...

which interacts with the mechanism of the

hair loss Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarring ...

linked endogenous

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

, '' CXXC5'', which is a negative feedback regulator of the Wnt/

β-catenin Catenin beta-1, also known as β-catenin (''beta''-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene. β-Catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcr ...

pathway''.'' Application of the peptide to bald

laboratory mice The laboratory mouse or lab mouse is a small mammal of the order Rodentia which is bred and used for scientific research or feeders for certain pets. Laboratory animal sources for these mice are usually of the species ''Mus musculus''. They a ...

resulted in new

hair follicle The hair follicle is an organ found in mammalian skin. It resides in the dermal layer of the skin and is made up of 20 different cell types, each with distinct functions. The hair follicle regulates hair growth via a complex interaction betwee ...

growth. PTD-DBM is a peptide activating the Wnt/β-catenin signaling pathway functioning via interference of the binding of CXXC5 to

Dishevelled Dishevelled (Dsh) is a family of proteins involved in canonical and non-canonical Wnt signalling pathways. Dsh (Dvl in mammals) is a cytoplasmic phosphoprotein that acts directly downstream of frizzled receptors. It takes its name from its initi ...

(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 Valproate (valproic acid, VPA, sodium valproate, and valproate semisodium forms) are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those with ...

(VPA), the activator of Wnt/β-catenin pathway, further induce hair re-growth as well as wound-induced hair neogenesis (WIHN). 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 Yonsei University () is a Private university, private Christian university, Christian research university located in Seoul, South Korea. Yonsei is one of the three most prestigious universities in the country, part of a group referred to as SK ...

in South Korea discovered a protein responsible for hair loss in the condition known as

androgenetic alopecia In botany, apomixis is asexual development of seed or embryo without fertilization. However, other definitions include replacement of the seed by a plantlet or replacement of the flower by bulbils. Apomictically produced offspring are genetic ...

. The responsible protein is called CXXC-type zinc finger protein 5 (CXXC5), which acts as a negative regulator for the Wnt/β-catenin pathway, involved in hair regeneration and wound healing. 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. 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). By topical application, PTD-DBM enhances hair regrowth as well as neogenesis. 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 Glycogen synthase kinase-3 beta, (GSK-3 beta), is an enzyme that in humans is encoded by the ''GSK3B'' gene. In mice, the enzyme is encoded by the Gsk3b gene. Abnormal regulation and expression of GSK-3 beta is associated with an increased susce ...

. Currently, topical application of PTD-DBM or its combination with VPA has been used for treatment of hair loss.

References

External links

"Korean Scientists Develop Potential Drug Candidate for Hair Loss"
- Business Korea Peptide therapeutics {{molecular-biology-stub