A Voyage on the Role of Nuclear Factor Kappa B (NF-kB) Signaling Pathway in Duchenne Muscular Dystrophy: An Inherited Muscle Disorder

Abstract

A recessive X-linked illness called Duchenne muscular dystrophy (DMD) is characterized by increasing muscle weakening and degradation. It primarily affects boys and is one of the most prevalent and severe forms of muscular dystrophy. Mutations in the DMD gene, which codes for the essential protein dystrophin, which aids in maintaining the stability of muscle cell membranes during contraction, are the cause of the illness. Dystrophin deficiency or malfunction damages muscle cells, resulting in persistent inflammation and progressive loss of muscular mass. The pathophysiology and genetic foundation of DMD are thoroughly examined in this review paper, focusing on the function of the NF-κB signaling system in the disease's progression. An important immune response regulator, NF-κB, is aberrantly activated in DMD, which exacerbates the inflammatory milieu in dystrophic muscles. Muscle injury and fibrosis are exacerbated and muscle regeneration is hampered by the pro-inflammatory cytokines and chemokines that are produced when NF-κB is persistently activated in muscle cells. The paper also examines our existing knowledge of treatment approaches meant to inhibit the progression of disease by modifying NF-κB signaling. These include new molecular techniques, gene treatments, and pharmacological inhibitors that are intended to lessen inflammation and improve muscle healing. Furthermore covered in the analysis is the significance of supportive care for DMD patients, including physical therapy and corticosteroid treatment, in symptom management and quality of life enhancement. The article seeks to provide a thorough understanding of the mechanisms causing DMD, possible therapeutic targets, and developing treatment options by combining recent research findings. This will provide clinicians and researchers involved in DMD care and research with invaluable insights.

Keywords: duchenne muscular dystrophy (dmd); dystrophin; fibrosis; glucocorticoids; inflammation; muscle degeneration; nf-κb signaling pathway.

Figure 1. This figure depicts the dystrophin-glycoprotein complex (DGC).

DGC connects muscle cell cytoskeletons to the extracellular matrix, providing structural stability to muscle fibers. Key components are: Collagen and laminin form the extracellular matrix, which provides structural support. Sarcospan and the sarcoglycan complex (α, β, γ, δ) are transmembrane proteins that maintain muscle integrity. Dystroglycans (α and β) connect the extracellular matrix to the cell membrane. Intracellular proteins: Dystrophin connects actin filaments to the sarcolemma, while dystrobrevin and syntrophins help with signaling and structural stability. Original illustration by the author.

Figure 2. The figure contrasts two NF-κB signaling pathways related to immune response and inflammation.

TNF-α, IL-1β, and LPS activate the canonical pathway, causing IκB degradation and NF-κB (p50/RelA) to enter the nucleus and activate genes. LT-α, CD40L, and BAFF activate a non-canonical pathway that involves NIK activation, p100 to p52 processing, and NF-κB (p52/RelB) entering the nucleus to regulate gene expression. Original illustration by the author.