PTD-DBM and Research Involving Hair Growth

PTD-DBM has been shown to promote Wnt/Beta-catenin signaling by inhibiting CXXC5 binding to Disheveled (Dvl), an upstream component of the Wnt/-catenin pathway.

Protein Transduction Domain-fused Disheveled Binding Motif (PTD-DBM) is a synthetic peptide that works in conjunction with CXXC5. This hair loss-linked endogenous protein acts as a negative feedback modulator of the Wnt/-catenin pathway.

The Mechanism of Action of PTD-DBM Peptide

CXXC5 acts as a reversible modulator on the Wnt/-catenin nerve tract, which is involved in wound healing and hair regrowth. It is known as the hair loss catalytic enzyme. CXXC5 forms a bond with the Dvl protein, which inhibits hair regeneration and follicle development. PTD-DBM prevents CXXC5 from binding to the disheveled protein. It works as a negative modulator of the entire process^[1]. When PTD-DBM prevents CXXC5 from becoming a disheveled protein, the Wnt/-catenin pathway is activated, inducing hair regrowth and wound-induced hair follicle neogenesis.

PTD-DBM inhibits the activities of body enzymes and hormones that shrink hair follicles, gradually restoring the strands at the stem cell level. PTD-DBM peptide prevents hair volume loss while stimulating the formation of new cavities for hair growth. 

Potential Functions

The most typical cause of hair loss, androgenetic alopecia, is permanent hair loss from the scalp. When PTD-DBM peptide is applied topically alone or in combination with local valproic acid, the chemical pathway that causes hair shrinkage is inhibited. The application of the peptide for six to twelve weeks results in the growth of newer and healthier hair follicles^[2]. This action is significant because new hair growth is consistent over time. 

PTD-DBM and Androgenetic Alopecia

The first side effects of Androgenetic Alopecia are the regression of the frontal hairline and hair loss in the vertex or crown region of the head. It progresses and causes total hair loss on the frontal and vertex scalps.

The anagen phase, catagen phase, and telogen phase are the three stages of hair growth. The anagen phase is shortened due to androgen hypersecretion, specifically testosterone. It causes hair to thin and fall out suddenly, and the anagen phase lasts only a few months.

The most crucial cellular pathway that regulates hair growth in hair follicles is the Wnt/-catenin pathway. Wnt proteins are released, which bind to the LDL-related protein LRP, deactivating glycogen synthase kinase-3 (GSK-3). GSK-3 inhibits -catenin’s actions in the hair follicle.

According to Professor Kang-Yell Choi’s research, CXXC-type zinc finger protein 5 (CXXC5) is expressed aggressively in the scalps of Alopecia patients^[3]. CXXC5 inhibits the Wnt/-catenin signaling pathway. CXXC5 accomplishes this by binding to the Dvl protein, hindering the growth and health of both new and existing hair follicles.

By inhibiting the actions of CXXC5 and Dvl protein, PTD-DBM reduces the prevalence of androgenetic alopecia, resulting in increased hair follicle growth and the anagen phase of the hair growth cycle. PTD-DBM actions result in healthier and more robust hair and less hair loss; when the peptide is in symbiosis with valproic acid, its potency increases. 

How PTD-DBM can Enhance the Rate of Wound Healing

The Wnt/-catenin signaling pathway is essential for wound healing and skin break fibrosis. The CXXC5 regulates it via a negative feedback mechanism. The CXXC5 binds to the Disheveled (Dvl) protein, inhibiting the Wnt/-catenin signaling pathway.

Inhibiting CXXC5 activities in mice promotes wound healing by stimulating collagen and keratin synthesis, specifically skin wound healing^[2].

Furthermore PTD-DBM inhibits the CXXC5-Dvl domain’s actions by preventing protein-to-protein interactions between CXXC5 and Dvl proteins. As a result, the Wnt/-catenin pathway becomes more active, inducing collagen and keratin synthesis and increased dermal fibrosis.

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References

1. Lee, S. H., Seo, S. H., Lee, D. H., Pi, L. Q., Lee, W. S., & Choi, K. Y. (2017). Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound-Induced Hair Neogenesis. The Journal of investigative dermatology, 137(11), 2260–2269. https://doi.org/10.1016/j.jid.2017.04.038
2. Lee SH, Kim MY, Kim HY, Lee YM, Kim H, Nam KA, Roh MR, Min do S, Chung KY, Choi KY. The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing. J Exp Med. 2015 Jun 29;212(7):1061-80. doi: 10.1084/jem.20141601. Epub 2015 Jun 8. PMID: 26056233; PMCID: PMC4493411.
3. Ryu YC, Lee DH, Shim J, Park J, Kim YR, Choi S, Bak SS, Sung YK, Lee SH, Choi KY. KY19382, a novel activator of Wnt/β-catenin signalling, promotes hair regrowth and hair follicle neogenesis. Br J Pharmacol. 2021 Jun;178(12):2533-2546. doi: 10.1111/bph.15438. Epub 2021 May 5. PMID: 33751552; PMCID: PMC8251890.
4. Rahman M, Nguyen H. Valproic Acid. [Updated 2022 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559112/