Therapeutic targeting of TIRAP: translating molecular insights into anti-inflammatory strategies against sepsis

Abstract

Sepsis owing to its complex nature still remains a difficult challenge in the medical community. The pathophysiology itself is what makes it so challenging to manage. The uncontrolled pathogenic load and the resulting dysregulated host immune response are the key reasons for its rapid widespread. The traditional approaches consist of the usage of monoclonal antibody, antibiotics, supportive care, and fluid resuscitation. Despite all these efforts sepsis still remains at the top for claiming millions of lives. One area that has not been much explored is the host targeted strategy. This paved the way for the current research work. We, investigate the role of TLR4 dependent TIRAP mediated pro-inflammatory immune signaling. TIRAP holding the top most position in the signaling cascade makes it an attractive and suitable target to explore. Not only has this but TIRAP’s ability to interact with various proteins also made it an approachable target. TIRAP is known to get phosphorylated and activated by the activity of two kinases. They comprise Protein Kinase C δ (PKCδ) and Bruton’s Tyrosine Kinase (BTK). An in depth analysis of TIRAP’s such interactions and its structural biology helped us to form a basic understanding of its working pattern.