Molecular mechanism and the main signaling pathways in the development and progression of multiple sclerosis

Abstract

Multiple sclerosis (MS) is a chronic, inflammatory central nervous system (CNS) disorder that often leads to significant disability, particularly in younger individuals. Its pathogenesis is thought to involve a complex interplay between genetic predispositions and environmental factors, culminating in CNS inflammation. Despite extensive research, treatment options for MS remain limited and often only partially effective. This review examines key signaling pathways implicated in MS progression, focusing on their potential as therapeutic targets. These pathways include the Fibroblast Growth Factor (FGF)/FGF receptor signaling, MAPK, NF-kB, JAK/STAT, Notch, mTOR, TGF-β, and PI3K/Akt pathways. The FGF pathway, particularly FGF2, plays a pivotal role in myelination and remyelination, while also contributing to neuroinflammation and disease exacerbation. Dysregulated MAPK/ERK signaling in microglia is associated with neurodegeneration, and NF-kB activation in glial cells promotes inflammation and demyelination. The JAK/STAT pathway is crucial for immune response regulation, with its dysregulation being a key factor in MS pathogenesis. Notch signaling regulates oligodendrocyte precursor cell differentiation, offering potential therapeutic advantages. mTOR and TGF-β signaling are essential for oligodendrocyte survival and tissue repair. Finally, the PI3K/Akt pathway is involved in cell survival and immune modulation, with applications in tissue engineering to enhance remyelination. These pathways provide valuable insights into MS mechanisms, highlighting novel therapeutic strategies.