Investigating How Inflammation Involving NF-κB Signaling Disrupts the Genetic Architecture of Neurons/Neural Stem Cells and Fuels Neurodegeneration

Abstract

Background: Understanding how inflammation disrupts neural stem cells and neuronal genetic architecture is crucial. This investigation explores these mechanisms, aiming to decipher the role of inflammation in disrupting neuronal genetic architecture. Unraveling these complexities may reveal therapeutic targets, offering hope for precision interventions to impede or slow the progression of debilitating neurodegenerative conditions.Methods: Databases including PubMed, MEDLINE and Google Scholar were searched for published articles without any date restrictions, involving NF-κB and neurogenic genes/signaling pathways/transcription factors. They were investigated in the study to unravel how inflammation disrupts the neural stem cells (NSCs) and neuronal genetic architecture, and how this process fuels the development of neurodegeneration. This study adheres to relevant PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses).Results: This study reveals how NF-κB activation plays a central role in inflammation-induced disruption, mediating transcriptional dysregulation of key neurogenic factors like Ngn1, NeuroD, and PDGF, compromising the neurogenic code. Downregulation of neurotrophic factors, notably BDNF, increases neuronal vulnerability to apoptotic pathways, accelerating neurodegeneration. Inflammatory processes extend to the genomic landscape, affecting genes crucial for neurogenesis and synaptic function, contributing to observed synaptic dysfunction in neurodegenerative diseases. Furthermore, inflammation disrupts NSCs, impairing neurogenesis and compromising neural progenitor dynamics, diminishing the regenerative potential of the nervous system. Identified therapeutic strategies include precision targeting of NF-κB, restoration of neurotrophic support, and interventions promoting proper gene expression and neurogenesis, offering promising avenues for mitigating inflammation-induced damage and halting neurodegenerative progression.Conclusion: This study investigates the intricate impact of inflammation on neural stem cells (NSCs) and neuronal genetic architecture, providing insights into the pathogenesis disrupting neuronal architecture. NF-κB-mediated disruptions compromise neurotrophic support, impair neurogenesis, induce synaptic dysfunction, and enhance vulnerability to apoptosis. This orchestrated genomic dysregulation contributes to the progression of neurodegenerative diseases. Therapeutically, precision targeting of NF-κB, restoration of neurotrophic support, and promotion of neurogenesis emerge as promising strategies to mitigate inflammation-induced damage, offering potential avenues for interventions to impede the neurodegenerative cascade.