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Updated: Jun 11, 2025

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
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Integrating protein interaction and pathway crosstalk network reveals a promising therapeutic approach for psoriasis

Masoumeh Farahani1, Reza M Robati2,3, Mostafa Rezaei-Tavirani4

  • 1Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Scientific Reports
|September 27, 2024
PubMed

Insights

This study reveals key protein interactions and pathways involved in psoriasis, identifying a crucial hub motif that drives disease complexity through pathway crosstalk. Targeting this crosstalk offers a promising therapeutic strategy for psoriasis.

Area of Science:

  • Dermatology
  • Immunology
  • Computational Biology

Background:

  • Psoriasis is a complex inflammatory skin disease characterized by abnormal keratinocyte proliferation, differentiation, and apoptosis.
  • Understanding the mechanisms of inefficient apoptosis is crucial for developing novel therapeutic strategies for psoriasis.

Purpose of the Study:

  • To identify regulatory factors and elucidate the mechanisms of inefficient apoptosis in psoriasis.
  • To generate a psoriasis-apoptosis interaction (SAI) network to uncover potential drug targets and therapeutic approaches.

Main Methods:

  • Construction and analysis of a psoriasis-apoptosis interaction (SAI) network using human protein interactions.
  • Application of network pharmacology, molecular docking, and molecular dynamics simulations to identify drug-target interactions.
  • Analysis of microarray datasets (GSE13355, GSE14905) and literature for experimental verification.

Main Results:

  • Identification of effective proteins including RELA, MAPK1, MAPK3, MMP9, IL1B, AKT1, and STAT1.
  • Discovery of the MAPK1-MAPK3-RELA motif as a central regulator of crosstalk among 41 pathways, with 'lipid and atherosclerosis' being predominant.
  • Identification of potential therapeutic drugs such as acetylcysteine, arsenic-trioxide, β-elemene, bortezomib, and curcumin.

Conclusions:

  • Hub motif-mediated pathway-pathway crosstalk, particularly involving apoptosis, significantly contributes to psoriasis complexity.
  • Inhibiting this crosstalk presents a viable and effective therapeutic approach for managing psoriasis.
Keywords:
ApoptosisDrugMolecular dynamics simulationPathway crosstalkProtein interactionPsoriasis

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