TY - JOUR
T1 - Re-Examining the Role of TNF in MS Pathogenesis and Therapy
AU - Fresegna, D.
AU - Bullitta, S.
AU - Musella, A.
AU - Rizzo, F.R.
AU - De Vito, F.
AU - Guadalupi, L.
AU - Caioli, S.
AU - Balletta, S.
AU - Sanna, K.
AU - Dolcetti, E.
AU - Vanni, V.
AU - Bruno, A.
AU - Buttari, F.
AU - Stampanoni Bassi, M.
AU - Mandolesi, G.
AU - Centonze, D.
AU - Gentile, A.
N1 - Export Date: 5 November 2020
PY - 2020
Y1 - 2020
N2 - Multiple sclerosis (MS) is a common neurological disorder of putative autoimmune origin. Clinical and experimental studies delineate abnormal expression of specific cytokines over the course of the disease. One major cytokine that has been shown to play a pivotal role in MS is tumor necrosis factor (TNF). TNF is a pleiotropic cytokine regulating many physiological and pathological functions of both the immune system and the central nervous system (CNS). Convincing evidence from studies in human and experimental MS have demonstrated the involvement of TNF in various pathological hallmarks of MS, including immune dysregulation, demyelination, synaptopathy and neuroinflammation. However, due to the complexity of TNF signaling, which includes two-ligands (soluble and transmembrane TNF) and two receptors, namely TNF receptor type-1 (TNFR1) and type-2 (TNFR2), and due to its cell- and context-differential expression, targeting the TNF system in MS is an ongoing challenge. This review summarizes the evidence on the pathophysiological role of TNF in MS and in different MS animal models, with a special focus on pharmacological treatment aimed at controlling the dysregulated TNF signaling in this neurological disorder.
AB - Multiple sclerosis (MS) is a common neurological disorder of putative autoimmune origin. Clinical and experimental studies delineate abnormal expression of specific cytokines over the course of the disease. One major cytokine that has been shown to play a pivotal role in MS is tumor necrosis factor (TNF). TNF is a pleiotropic cytokine regulating many physiological and pathological functions of both the immune system and the central nervous system (CNS). Convincing evidence from studies in human and experimental MS have demonstrated the involvement of TNF in various pathological hallmarks of MS, including immune dysregulation, demyelination, synaptopathy and neuroinflammation. However, due to the complexity of TNF signaling, which includes two-ligands (soluble and transmembrane TNF) and two receptors, namely TNF receptor type-1 (TNFR1) and type-2 (TNFR2), and due to its cell- and context-differential expression, targeting the TNF system in MS is an ongoing challenge. This review summarizes the evidence on the pathophysiological role of TNF in MS and in different MS animal models, with a special focus on pharmacological treatment aimed at controlling the dysregulated TNF signaling in this neurological disorder.
U2 - 10.3390/cells9102290
DO - 10.3390/cells9102290
M3 - Article
C2 - 33066433
VL - 9
JO - Cells
JF - Cells
SN - 2073-4409
IS - 10
ER -