Curcumin alleviates depression-aggravated psoriasis by targeting MMP9-regulated apoptotic pathways.

Area of Science:

• Biomedical Science
• Genetics
• Dermatology

Background:

• Depression and psoriasis frequently co-occur, but underlying molecular connections are unclear.
• Understanding shared mechanisms is crucial for effective treatment strategies.

Purpose of the Study:

• To investigate the molecular links between depression and psoriasis.
• To identify causal genes and pathways involved in their comorbidity.
• To explore potential therapeutic interventions targeting shared mechanisms.

Main Methods:

• Cross-sectional analysis of NHANES data and Mendelian randomization (MR).
• Development of a combined mouse model simulating chronic stress and psoriasis.
• Integrated multi-omics analyses including RNA sequencing and machine learning.
• Molecular docking and in vivo experiments with curcumin.

Main Results:

• A significant association and causal link between depression and psoriasis were identified.
• Apoptosis emerged as a key shared pathway, with MMP9 identified as a central causal gene.
• MMP9 upregulation was confirmed in both skin and brain tissues in the mouse model.
• Curcumin treatment downregulated MMP9 and ameliorated symptoms of both depression and psoriasis.

Conclusions:

• MMP9-mediated apoptosis is a critical molecular link in the comorbidity of depression and psoriasis.
• Targeting MMP9 offers a potential dual-treatment strategy for patients with both conditions.