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Involvement of IL-1R/TLR Signalling in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis

[ Vol. 12 , Issue. 3 ]

Author(s):

V. Ruggiero   Pages 218 - 236 ( 19 )

Abstract:


Multiple sclerosis is a complex disease characterised by chronic inflammation, demyelination and axonal pathology resulting in progressive neurological disabilities. Multiple sclerosis is generally considered to be an autoimmune disease, even though the primary cause of the underlying autoimmune response is unknown. Epidemiological evidence suggests that both genetic and environmental factors play a key role in susceptibility to multiple sclerosis; however, the relative contributions of these factors in triggering the onset of the disease remain unclear. Several studies indicate that receptors belonging to the Interleukin-1 and Toll-like receptor families are crucially involved in the mechanisms underlying the development of experimental autoimmune encephalomyelitis, an animal model that mimics multiple sclerosis. Moreover, recent evidence highlights the importance of downstream signalling proteins in the Interleukin-1 and Toll-like receptor signalling pathways, namely, myeloid differentiation primary response protein 88 and Interleukin-1-receptor-associated kinase. This review summarises the current knowledge concerning the involvement of Interleukin-1/Toll-like receptor signalling in the development of experimental autoimmune encephalomyelitis and multiple sclerosis. A deeper understanding of the role of these important pathways in the pathogenesis of experimental autoimmune encephalomyelitis may eventually yield clinical benefits in the treatment of central nervous system-based inflammatory disorders.

Keywords:

Experimental autoimmune encephalomyelitis, innate immunity, interleukin-1 receptor, microglia, multiple sclerosis, neuroinflammation, toll-like receptor, blood-brain barrier, inflammatory reactions, demyelination, axonal degeneration, tissue repair, homeostasis, neurodegeneration, astrocytes

Affiliation:

Sigma-tau Industrie Farmaceutiche Riunite S.p.A., Department of Immunology (Bldg. LABIO), via Pontina km 30.400, 00040 Pomezia (RM), Italy.



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