The NF ‐ κB Signalling Pathway: Mechanisms, Consequences and Therapeutic Targets
- 1Medical Biotechnology Department, Mashhad Medical School Mashhad University of Medical Sciences Mashhad Iran
- 2Department of Laboratory Sciences, School of Paramedical Sciences Mashhad University of Medical Sciences Mashhad Iran
Abstract
Nuclear Factor-kappa B (NF-κB) is a master transcriptional regulator orchestrating critical cellular processes, predominantly immunity and inflammation. However, its aberrant constitutive activation has emerged as a unifying pathogenetic hallmark across diverse malignancies, autoimmune disorders, and chronic inflammatory diseases. While the fundamental biology of canonical and non-canonical NF-κB signalling is well-established, translating this extensive knowledge into clinically viable therapeutics remains severely hindered by dose-limiting systemic toxicities and complex pharmacokinetic liabilities. This review critically evaluates the transition of NF-κB from a basic biological paradigm to a highly challenging yet promising therapeutic target. After a streamlined synthesis of its signalling dynamics and pathological implications across various disease states, the core focus of this report shifts to an in-depth analysis of next-generation therapeutic interventions. We specifically dissect advanced molecular strategies, moving beyond conventional pharmacological inhibitors to emphasize nucleic acid-based therapies, including decoy oligodeoxynucleotides (ODNs), peptide nucleic acids (PNAs), and locked nucleic acids (LNAs). Furthermore, we critically address current translational bottlenecks, highlighting the pivotal role of lipid nanoparticle (LNP) transporters and smart drug delivery systems in overcoming off-target effects. By mapping these cutting-edge modalities, this review underscores the critical necessity of transitioning from broad-spectrum inhibition toward context-specific, precision-engineered modulation of the NF-κB axis.
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BibTeX
@article{pourdad2026signalling,
title = {{The NF ‐ κB Signalling Pathway: Mechanisms, Consequences and Therapeutic Targets}},
author = {Bherouz Pourdad and Arash Pourdad},
journal = {Journal of Cellular and Molecular Medicine},
year = {2026},
month = jun,
doi = {10.1111/jcmm.71229},
url = {https://doi.org/10.1111/jcmm.71229},
note = {CC BY},
}
RIS
TY - JOUR
TI - The NF ‐ κB Signalling Pathway: Mechanisms, Consequences and Therapeutic Targets
AU - Bherouz Pourdad
AU - Arash Pourdad
PY - 2026
DA - 2026/06/01
JO - Journal of Cellular and Molecular Medicine
DO - 10.1111/jcmm.71229
UR - https://doi.org/10.1111/jcmm.71229
AB - Nuclear Factor-kappa B (NF-κB) is a master transcriptional regulator orchestrating critical cellular processes, predominantly immunity and inflammation. However, its aberrant constitutive activation has emerged as a unifying pathogenetic hallmark across diverse malignancies, autoimmune disorders, and chronic inflammatory diseases. While the fundamental biology of canonical and non-canonical NF-κB signalling is well-established, translating this extensive knowledge into clinically viable therapeutics remains severely hindered by dose-limiting systemic toxicities and complex pharmacokinetic liabilities. This review critically evaluates the transition of NF-κB from a basic biological paradigm to a highly challenging yet promising therapeutic target. After a streamlined synthesis of its signalling dynamics and pathological implications across various disease states, the core focus of this report shifts to an in-depth analysis of next-generation therapeutic interventions. We specifically dissect advanced molecular strategies, moving beyond conventional pharmacological inhibitors to emphasize nucleic acid-based therapies, including decoy oligodeoxynucleotides (ODNs), peptide nucleic acids (PNAs), and locked nucleic acids (LNAs). Furthermore, we critically address current translational bottlenecks, highlighting the pivotal role of lipid nanoparticle (LNP) transporters and smart drug delivery systems in overcoming off-target effects. By mapping these cutting-edge modalities, this review underscores the critical necessity of transitioning from broad-spectrum inhibition toward context-specific, precision-engineered modulation of the NF-κB axis.
SN - 1582-1838
SN - 1582-4934
ER -