Two decades and beyond: What we know and still need to learn about the TWEAK/Fn14 pathway

Area of Science:

• Molecular Biology
• Cell Signaling
• Immunology

Background:

• TWEAK, a cytokine, interacts with its receptor Fn14, activating downstream pathways like MAPK and NF-κB.
• This TWEAK/Fn14 signaling cascade is implicated in diseases affecting cardiovascular, pulmonary, dermatological, and cancer systems.
• The precise roles and mechanisms of the TWEAK/Fn14 pathway in various diseases remain incompletely understood.

Purpose of the Study:

• To systematically review the structural, functional, and pharmacological aspects of the TWEAK/Fn14 signaling pathway.
• To highlight the necessity of further research into the molecular mechanisms of this pathway.
• To explore the potential of small molecules targeting the TWEAK/Fn14 cascade for future disease management.

Main Methods:

• Systematic literature review.
• Analysis of existing research on TWEAK/Fn14 signaling.
• Identification of knowledge gaps and future research directions.

Main Results:

• The TWEAK/Fn14 pathway regulates critical cellular processes including differentiation, proliferation, angiogenesis, apoptosis, and autophagy.
• Activation of this pathway leads to cytokine and chemokine production, influencing intercellular communication.
• Challenges in clinical translation include a lack of biomarkers and disease heterogeneity.

Conclusions:

• The TWEAK/Fn14 pathway is a critical regulator of cell fate with significant implications in various diseases.
• Further experimental research is essential to elucidate the complex molecular mechanisms involved.
• Targeting the TWEAK/Fn14 signaling cascade with small molecules presents a promising therapeutic avenue for diverse diseases.