Cullin-3 and Regulatory Biomolecules Profiling in Vitiligo: Integrated Docking, Clinical, and In Silico Insights

Area of Science:

• Dermatology
• Molecular Biology
• Immunology

Background:

• Vitiligo is a chronic depigmentation disorder linked to oxidative stress and immune dysregulation.
• The Keap1/NRF2/ARE pathway is crucial for melanocyte protection, but the role of Cullin-3 (CUL3) in vitiligo is unclear.
• This study explores CUL3, NRF2, and related inflammatory pathways in vitiligo pathogenesis.

Purpose of the Study:

• Investigate the role of CUL3, NRF2, and associated regulatory networks in vitiligo.
• Identify potential therapeutic targets by integrating clinical data and computational analysis.
• Examine the interplay between the CUL3/Keap1/NRF2 axis and inflammatory mediators in vitiligo.

Main Methods:

• A case-control study compared vitiligo patients with healthy controls.
• Quantitative real-time PCR (qRT-PCR) analyzed gene and miRNA expression in skin biopsies.
• Molecular docking evaluated vitexin's binding affinity to Keap1.

Main Results:

• Vitiligo patients showed decreased expression of CUL3, NRF2, and FOXP3.
• Elevated levels of miRNA-146a, NF-κB, IL-6, and TNF-α were observed in vitiligo patients.
• Molecular docking demonstrated strong binding of vitexin to Keap1.

Conclusions:

• CUL3/Keap1/NRF2 axis dysregulation and increased miRNA-146a correlate with vitiligo progression.
• Vitexin's interaction with Keap1 suggests potential for modulating the NRF2 pathway in vitiligo.
• Targeting the ubiquitin-proteasome and antioxidant pathways offers therapeutic potential for vitiligo management.