Decoding the Crosstalk: Canonical and Non-Can...

Decoding the Crosstalk: Canonical and Non-Canonical NF-ΚB Pathways in Health and Disease

Author Name : Mohd. Sayam, Tichakunda Xavier Mharazanye, Steven Joseph Nkuku, Abu Sufiyan Ansari, Kundan Kumar, Himanshu Rawat, Subodh kumar, Sujit Kumar Barnwal

ABSTRACT NF-kB is a crucial signaling pathway that regulates host inflammatory and immune responses, preventing cellular apoptosis. It enhances gene expression for cytokines, chemokines, and receptors involved in neutrophil adhesion and migration. Cytokines like IL-1b and TNFα can initiate the NF-kB pathway, contributing to chronic inflammation. NF-kB regulates B- lymphocyte functions and cytokine-induced proliferation of T lymphocytes. The homology domain is essential for DNA binding, dimerization, and nuclear translocation. The phosphorylation of IkB proteins is a critical regulatory step in the NF-kB pathway. The non- canonical NF-κB pathway is significant in cancer progression and metastasis, fostering cell proliferation and survival while inhibiting apoptosis. It modulates pro-inflammatory cytokines and chemokines, creating a microenvironment conducive to tumor growth. It also facilitates angiogenesis, a process crucial for tumor development and metastasis. Activation of this pathway may result in resistance to chemotherapy and radiotherapy. Therapeutic strategies include inhibitors targeting key components, addressing downstream effectors, and modulating the immune response. Combination therapies, gene editing technologies, and nanoparticle delivery systems are being investigated to counteract resistance and enhance treatment efficacy.