Chonnam Med J.  2019 May;55(2):75-85. 10.4068/cmj.2019.55.2.75.

Therapeutic Effects of Synthetic Antimicrobial Peptides, TRAIL and NRP1 Blocking Peptides in Psoriatic Keratinocytes

Affiliations
  • 1Department of Dermatology, University of Colorado Denver School of Medicine, Aurora, CO, USA. peter.song@ucdenver.edu
  • 2Department of Biomedical Science and Research Center for Proteinaceous Materials, Chosun University School of Medicine, Gwangju, Korea.
  • 3Department of Biology, University of Denver, Denver, CO, USA.
  • 4Department of Dermatology, Chung-Ang University School of Medicine, Seoul, Korea.

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.

Keyword

Psoriasis; Anti-Bacterial Agents; TNF-Related Apoptosis-Inducing Ligand; Neuropilin-1

MeSH Terms

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
Anti-Bacterial Agents
Biological Factors
Neuropilin-1
Peptides
Receptors, Death Domain
Semaphorins
TNF-Related Apoptosis-Inducing Ligand
Therapeutic Uses
Vascular Endothelial Growth Factor A
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