title: A further TWEAK to multiple sclerosis pathophysiology.
abstract: Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a member of the TNF super family that controls many cellular activities including proliferation, migration, differentiation, apoptosis, and inflammation by binding to fibroblast growth factor-inducible 14 (Fn14), a highly inducible cell surface receptor. Recent studies have indicated that TWEAK-Fn14 axis signaling may contribute to chronic autoimmune diseases. TWEAK expression via microglia in cortical lesions, presence of TWEAK(+) macrophages in inflamed leptomeninges, and absence of TWEAK/Fn14 expression in healthy brain implicates importance of this pathway in pathogenesis of multiple sclerosis lesions. TWEAK-Fn14 axis blockade has also shown promise in various multiple sclerosis animal models. Stimulation of the TWEAK/Fn14 pathway can result in activation of both canonical and noncanonical NF-κB signaling and could also stimulate mitogen-activated protein kinase (MAPK) signaling pathways. Here, we have reviewed evidence of the possible role of TWEAK-Fn14 axis in pathophysiology of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) via neuroinflammation, tissue remodeling, blood-brain barrier (BBB) disruption, neurodegeneration, and astrogliosis.
authors.affiliation: Interdisciplinary Neuroscience Research Program, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Arash
authors.initials: A
authors.lastname: Nazeri
authors.forename: Pouria
authors.initials: P
authors.lastname: Heydarpour
authors.forename: Shokufeh
authors.initials: S
authors.lastname: Sadaghiani
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Sahraian
authors.forename: Linda C
authors.initials: LC
authors.lastname: Burkly
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
mesh_terms: D000818:Animals; D002465:Cell Movement; D000074049:Cytokine TWEAK; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D000074050:TWEAK Receptor; D048069:Tumor Necrosis Factors / Q000378:metabolism / Q000502:physiology*
chemical_list: D000074049:Cytokine TWEAK; D018124:Receptors, Tumor Necrosis Factor; C000613297:TNFRSF12A protein, human; C109743:TNFSF12 protein, human; D000074050:TWEAK Receptor; C000613300:Tnfrsf12a protein, rat; D048069:Tumor Necrosis Factors