Recent developments in aesthetic dermatology are revealing how much the skin shares with the nervous system—not only in terms of embryologic origin, but also in molecular signaling. Among the most intriguing discoveries is the presence of functional N-methyl-D-aspartate (NMDA) receptors in epidermal cells, and how their activation may influence keratinocyte growth, differentiation, and skin barrier homeostasis. This article explores the significance of these findings and how they support the mechanism of action of PRX PLUS, a non-injectable topical skin booster containing homocysteic acid, a selective NMDA receptor agonist.

NMDA Receptors in Keratinocytes and Melanocytes
Initially characterized within the central nervous system, NMDA receptors are classified as ionotropic glutamate receptors, recognized for their capacity to facilitate calcium influx. Nonetheless, research conducted in the early 2000s commenced the documentation of their expression in non-neuronal tissues, most notably in the epidermis.

In 2004, Morhenn et al. illustrated the presence of NMDA receptors on human keratinocytes within both healthy and psoriatic skin, indicating that the activation of these receptors influences calcium influx and subsequently impacts cell proliferation and apoptosis. Likewise, Nahm et al. (2004) validated that skin injury induces a polarization of NMDA receptor expression, thereby associating it with the process of re-epithelialization.

Notably, Fuziwara and Denda (2003) reported that topical application of NMDA agonists delays barrier repair, while NMDA antagonists accelerate it—emphasizing the receptor’s regulatory role in cutaneous barrier recovery.

A New Player: Homocysteic Acid
PRX PLUS is currently the first aesthetic formula on the market to include homocysteic acid (HoA), a naturally occurring sulfur-containing amino acid and endogenous NMDA receptor agonist.

It has been demonstrated that homocysteic acid:

Selectively open NMDA receptor-gated calcium channels;
Initiate signaling pathways associated with cell migration and differentiation;
Influence pigment transfer in melanocytes via cytoskeletal remodeling.
This positions HoA as a biologically active, non-cytotoxic modulator of skin cell function—particularly relevant in the context of controlled skin regeneration without inflammation.

Mechanistic Considerations for Aesthetic Use
From a clinical viewpoint, the inclusion of homocysteic acid in PRX PLUS gives a scientifically legitimate explanation for a range of observed effects:

Improved skin texture and microroughness
Visible minimization of pores and fine lines
Brightening and evening of complexion
These alterations are associated with keratinocyte turnover and matrix remodeling, which are probably caused by NMDA receptor-mediated Ca²⁺ entry that stimulates downstream signaling cascades that regulate regeneration and cell-cell communication.

Empirical Evidence Based on Clinical Studies
In a study of 30 women, PRX PLUS greatly enhanced:

Skin roughness (-30.2%)
Wrinkle depth (-40.4%)
Pore size (-46.5%)
Pigmentation irregularities (reduction of UV spots -10.7%)
— after just three weekly treatments, without any exfoliation and without any reported side effects. These findings are consistent with the predicted biological reactions of keratinocytes and melanocytes to disrupted NMDA signaling, as supported by in vitro and in vivo experiments.

Conclusion: A Rational Approach to Non-Invasive Skin Regeneration

The application of NMDA receptor biology to topical skin treatment is a significant advancement in aesthetic medicine. In contrast to conventional peeling or injectable methods, PRX PLUS provides a physiological, receptor-targeted approach for dermal remodeling stimulation, without barrier compromise or inflammation.

As practitioners, knowing the receptor-level pharmacodynamics of what we use enables us to transcend empirical outcomes—and communicate in the same language as contemporary dermatological science.

References:
Morhenn V. et al. (2004). Exp Dermatol 13:505–511.
Fuziwara, S., et al. (2003). Journal of Investigative Dermatology, 120: 1023–1029.
Nahm, W., et al. (2004). Journal of Cell Physiology, 200, 309–317.
Ni J. et al. (2016). J Dermatol Sci, doi:10.1016/j.jdermsci.2016.08.534 Internal clinical dossier,
Report_PRX_Plus.pdf, WiQo Scientific Division.
PRX PLUS Product Presentation, WiQo, 2024.