Signaling pathways and targeted therapy for rosacea.

Area of Science:

• Dermatology
• Immunology
• Molecular Biology

Background:

• Rosacea is a prevalent chronic inflammatory skin condition affecting 1-20% globally.
• Characterized by facial redness, visible blood vessels, papules, pustules, and eye issues.
• Pathogenesis is multifactorial, involving genetics, environment, immunity, microbes, and neurovascular elements.

Purpose of the Study:

• To review current knowledge on molecular signaling pathways in rosacea.
• To explore the role of specific pathways like TLR2, LL37, mTOR, IL-17, TRPV, and JAK-STAT.
• To discuss potential targeted therapeutic strategies based on these pathways.

Main Methods:

• Literature review of recent studies on rosacea molecular pathogenesis.
• Analysis of signaling pathways including toll-like receptor 2 (TLR2), LL37, mammalian target of rapamycin (mTOR), interleukin-17 (IL-17), transient receptor potential vanilloid (TRPV), and Janus kinase-signal transducer and activator of transcription (JAK-STAT).
• Examination of molecular interactions and downstream effects on immune cells and vascular factors.

Main Results:

• LL37-associated pathways, particularly TLR2 and mTORC1, are central to rosacea pathogenesis.
• Interactions involve ERK1/2, NF-κB, inflammasomes, CXCL8, MRGPRX2-TRPV4, and VEGF, activating immune cells and leading to cytokine release (TNF-α, IL-6, IL-1β, CCL5, CXCL9, CXCL10).
• IL-17 and JAK/STAT pathways significantly contribute to inflammation and angiogenesis in rosacea.

Conclusions:

• Understanding these signaling pathways is crucial for elucidating rosacea pathophysiology.
• Targeted therapies, including cytokine inhibitors, IL-17 inhibitors, JAK inhibitors, and VEGF antagonists, show promise for improved rosacea treatment.
• Future therapies aim for greater efficacy and reduced side effects by targeting specific molecular pathways.