Alopecia is a common form of hair loss that affects both men and women, and typically becomes more severe with age. Emerging evidence has implicated oxidative stress in the pathogenesis of this condition.
Human dermal papilla cells (hDPCs) are pivotal for hair follicle development and regeneration. By secreting growth-promoting signals, hDPCs play an essential role in regulating the hair growth cycle.
Research has indicated that hydrogen peroxide is involved in damaging hDPCs, ultimately leading to hair loss.
In a study co-funded by South Korea’s Ministry of Health and Welfare and biotech firm Innovo Therapeutics, researchers developed a pan-caspase inhibitor called THPA and investigated its potential in reducing reactive oxygen species (ROS)-induced cellular damage and apoptosis in hDPCs.
Caspases are a family of protease enzymes that are important for maintaining homeostasis by regulating cell death and inflammation, and their inhibition contributes to the prevention of cell death.
During the study, hydrogen peroxide was used to induce oxidative stress in hDPCs.
The results showed that THPA effectively suppressed hydrogen peroxide-induced apoptosis by regulating caspase signalling activated by oxidative stress.
Additionally, THPA restored the down-regulated expression of beta-catenin (β-catenin), the primary mediator of the Wnt/β-catenin signalling pathway, in hDPCs exposed to hydrogen peroxide.
The Wnt/β-catenin signalling pathway is crucial for the regeneration of hair follicles and growth of hair shafts. Studies have shown that the inhibition of β-catenin hinders the hair growth cycle, whereas its activation promotes hair growth and prolongs the anagen phase.
“Hydrogen peroxide reduced the protein expressions of β-catenin, which affects hair growth. We found that this decrease was prevented by THPA pre-treatment,” the authors wrote.
Furthermore, significant alterations in the Akt/mTOR/p70S6K signalling pathway were observed following THPA treatment. This includes a reduction in the expression of Dickkopf-1 (DKK-1) protein, which is associated with hair follicle regression.
“Compared to non-balding scalp tissues, the expression of DKK-1 in balding scalp tissues is elevated. Therefore, our data suggest that THPA promotes hair growth by potentially inhibiting the entry into the catagen phase through down-regulating the level of DKK-1.
“To date, a hair loss treatment utilising a caspase inhibitor has not been commercialised. Our findings highlight the potential of THPA as a new therapy for preventing cell senescence and premature onset of the catagen phase by protecting hDPCs against oxidative stress damage.”
Delay cell damage
Higher ROS levels have been detected in the hDPCs of balding scalps than in non-balding scalps, with elevated ROS levels correlating with reduced hDPCs motility and heightened cell senescence.
These findings suggest that targeting ROS is a promising approach in the development of alopecia prevention and treatment strategies.
“The effects of THPA are related to its antioxidative properties. The up-regulation of intracellular ROS levels mediated by hydrogen peroxide was dramatically inhibited following THPA pre-treatment.
“Moreover, THPA can prevent the apoptosis of hDPCs by ROS-induced Akt/mTOR/p70S6K activation, indicating that the Akt/mTOR/p70S6K signalling cascade may be the potential mechanism for hair loss.”
In addition, the study observed that exposure to hydrogen peroxide resulted in a marked increase in the protein expression of cell senescence markers p21 and p16, which was significantly reduced through THPA treatment.
“This underscores the potential of THPA in preserving hDPC function and delaying hair follicle regression. Therefore, we propose that THPA should be further investigated in clinical trials to substantiate its potential for preventing hair loss by elucidating its underlying mechanisms.”
Source: Cosmetics
https://doi.org/10.3390/cosmetics11040105
“The Inhibition of Oxidative Stress-Mediated Cell Apoptosis by the Caspase Inhibitor (S)-3-((S)-2-(6-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-oxoisoindolin-2-yl)butanamido)-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic Acid in Human Dermal Papilla Cells”
Authors: Bomi Park, et al