New GPER1 receptor discovery could revolutionize psoriasis treatment strategies

A new study published in Cell Death Discovery highlights the potential of G protein-coupled estrogen receptor 1 (GPER1) in treating skin inflammation. Researchers found that activating GPER1 slows down keratinocyte proliferation, a key factor in conditions like psoriasis. The discovery suggests fresh avenues for developing targeted therapies.

The study identified GPER1 as a critical regulator of skin cell growth. When activated, the receptor significantly reduces keratinocyte proliferation, particularly during the G1 phase of the cell cycle. This effect stems from its interference with the MAPK/ERK pathway, which lowers the production of pro-inflammatory mediators such as TNF-α and IL-6.

In preclinical tests, mice with imiquimod-induced psoriasis-like inflammation received topical applications of the GPER1 agonist G-1. The treatment led to marked improvements, including reduced skin thickening, scaling, and lower levels of inflammatory cytokines like IL-17 and IL-23. These results suggest that GPER1 agonists could effectively manage disease severity and histopathological features in inflammatory skin conditions.

Unlike classical nuclear estrogen receptors, GPER1 triggers rapid cellular responses linked to estrogen signalling. Its distinct mechanism offers a more selective approach to treatment, potentially improving safety profiles compared to existing therapies. The findings also highlight the broader role of G protein-coupled receptors (GPCRs) in skin health and disease.

The study opens doors for new topical or systemic treatments targeting GPER1. Assessing receptor levels or functionality could further personalise therapies for patients with skin diseases. Such innovations may lead to better disease management and improved quality of life for those affected.