Therapeutic Effects of Synthetic Antimicrobial Peptides, TRAIL and NRP1 Blocking Peptides in Psoriatic Keratinocytes
- Author:
Sunhyo RYU
1
;
Lindsey BROUSSARD
;
Chakyung YOUN
;
Brendon SONG
;
David NORRIS
;
Cheryl A ARMSTRONG
;
Beomjoon KIM
;
Peter I SONG
Author Information
- Publication Type:Review
- Keywords: Psoriasis; Anti-Bacterial Agents; TNF-Related Apoptosis-Inducing Ligand; Neuropilin-1
- MeSH: Anti-Bacterial Agents; Bacteria; Biological Factors; Endothelial Cells; Keratinocytes; Necrosis; Neuropilin-1; Peptides; Psoriasis; Receptors, Death Domain; Recurrence; Semaphorins; Skin; Skin Diseases; Staphylococcus; Staphylococcus aureus; Therapeutic Uses; TNF-Related Apoptosis-Inducing Ligand; United States; Vascular Endothelial Growth Factor A
- From:Chonnam Medical Journal 2019;55(2):75-85
- CountryRepublic of Korea
- Language:English
- Abstract: Psoriasis is a chronic, recurrent, heterogeneous, cutaneous inflammatory skin disease for which there is no cure. It affects approximately 7.5 million people in the United States. Currently, several biologic agents that target different molecules implicated in the pathogenic processes of psoriasis are being assessed in diverse clinical studies. However, relapse usually occurs within weeks or months, meaning there is currently no cure for psoriasis. Therefore, recent studies have discovered diverse new potential treatments for psoriasis: inhibitors of bacteria such as Staphylococcus aureus, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and neuropilin 1 (NRP1). A promising approach that has recently been described involves modifying antimicrobial peptides to develop new cutaneous anti-bacterial agents that target inflammatory skin disease induced by Staphylococcus. Increased expression of TRAIL and its death receptors DR4 and DR5 has been implicated in the pathogenesis of plaque psoriasis. In addition, TRAIL has the ability to inhibit angiogenesis by inducing endothelial cell death and by negative regulation of VEGF-induced angiogenesis via caspase-8-mediated enzymatic and non-enzymatic functions. Since NRP1 regulates angiogenesis induced by multiple signals, including VEGF, ECM and semaphorins, and also initiates proliferation of keratinocytes through NF-κB signaling pathway in involved psoriatic skin, targeting NRP1 pathways may offer numerous windows for intervention in psoriasis. In this review, we will focus on the current knowledge about the emerging role of synthetic antimicrobial peptides, TRAIL and NRP1 blocking peptides in the pathogenesis and treatment of psoriasis.
