Guardians of Immunity: Toll-Like Receptor Signalling in the Onset and Progression of Multiple Sclerosis, Sketching an Immunopathological Scheme
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Abstract
Background: Multiple Sclerosis (MS) is a chronic autoimmune disorder of the central nervous system, characterized by inflammation, demyelination, and neurodegeneration. The role of toll-like receptors (TLRs) in MS pathogenesis, specifically through MYD88-dependent and -independent pathways, has become a focal point of research. Understanding these pathways offers insights into the mechanisms driving MS and potential therapeutic targets.
Objective: This review aims to synthesize current knowledge on the role of TLR signaling in the onset and progression of MS, focusing on the dysregulation of MYD88-dependent and -independent pathways and their implications for disease pathogenesis and therapy.
Methods: A systematic search of PubMed, Scopus, Web of Science, and Google Scholar databases was conducted to identify studies related to TLR signaling in MS. Keywords related to "toll-like receptors," "multiple sclerosis," "MYD88-dependent pathway," "MYD88-independent pathway," and "immune response" were used. The evidence synthesis was qualitative, integrating findings from both human and animal studies.
Results: The review highlights the central role of NF-kB in mediating the effects of TLR signaling on the inflammatory cascade in MS. Dysregulation in TLR signaling pathways can lead to increased expression of pro-inflammatory cytokines and compromise the blood-brain barrier, exacerbating MS pathogenesis. The evidence points towards the dual role of TLR pathways in promoting inflammatory responses and potentially offering protective mechanisms against the disease.
Conclusion: TLR signaling pathways play a crucial role in the immunopathology of MS, with both MYD88-dependent and -independent pathways contributing to disease progression. Targeting these pathways presents a promising therapeutic strategy, emphasizing the need for further research to develop effective treatments.
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