PTD-DBM as a potential hairloss treatment

[fluoride1337]

CXXC5 Mediates DHT-Induced Androgenetic Alopecia via PGD2​

The hair loss by PGD2 was restored by Cxxc5 knock-out or treatment of protein transduction domain–Dishevelled binding motif (PTD-DBM), a peptide activating the Wnt/β-catenin pathway via interference with the Dishevelled (Dvl) binding function of CXXC5. In addition, suppression of neogenic hair growth by PGD2 was also overcome by PTD-DBM treatment or Cxxc5 knock-out as shown by the wound-induced hair neogenesis (WIHN) model. Moreover, we found that CXXC5 also mediates DHT-induced hair loss via PGD2. DHT-induced hair loss was alleviated by inhibition of both GSK-3β and CXXC5 functions. Overall, CXXC5 mediates the hair loss by the DHT-PGD2 axis through suppression of Wnt/β-catenin signaling.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9954685/

Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound-Induced Hair Neogenesis​

CXXC5 was upregulated in miniaturized hair follicles and arrector pili muscles in human balding scalps. The inhibitory effects of CXXC5 on alkaline phosphatase activity and cell proliferation were demonstrated using human hair follicle dermal papilla cells. Moreover, CXXC5−/− mice displayed accelerated hair regrowth, and treatment with valproic acid, a glycogen synthase kinase 3β inhibitor that activates the Wnt/β-catenin pathway, further induced hair regrowth in the CXXC5−/− mice. Disrupting the CXXC5-Dishevelled interaction with a competitor peptide activated the Wnt/β-catenin pathway and accelerated hair regrowth and wound-induced hair follicle neogenesis. Overall, these findings suggest that the CXXC5-Dishevelled interaction is a potential target for the treatment of hair loss.

https://www.sciencedirect.com/science/article/pii/S0022202X17315555

(Using different compound to inhibit CXXC5)

KY19382, a novel activator of Wnt/β-catenin signalling, promotes hair regrowth and hair follicle neogenesis​

KY19382 activated Wnt/β-catenin signalling and elevated expression of ALP and the proliferation marker PCNA in DP cells. KY19382 also increased hair length in ex vivo-cultured mouse vibrissa and human hair follicles and induced hair regrowth in mice. Moreover, KY19382 significantly promoted the generation of de novo hair follicles as shown by WIHN and hair patch assays.

https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.15438