Tumor necrosis factor superfamily in multiple sclerosis: from pathology to therapeutic implications
Published: May 3 2023
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Tumor necrosis factor (TNF) is a key player in multiple sclerosis pathology. TNF signaling is dually regulated by antagonist groups of actors: TNFR1, mediating proinflammatory effects and synaptopathy, CD40L-CD40 dyad, crucial for blood-brain barrier breakdown and facilitation of recruitment of inflammatory cells in the central nervous system, and TNFR2, promoting neuroprotective and reparative functions. A promising therapeutic approach in multiple sclerosis is represented by selective TNFR1 antagonists and TNFR2 agonists, possibly in combination. TNFR2 agonists could exert both central effects such as remyelination, reduction of glutamatergic excitotoxicity, and peripheral immunomodulation by enhancing T cells (Treg) activity. On the other side, the potential therapeutic role of platelet and CD40L-CD40 dyad inhibition could be beneficial to preserve blood-brain barrier integrity and thereby dampen neuroinflammation.
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Citations
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How to Cite
Tumor necrosis factor superfamily in multiple sclerosis: from pathology to therapeutic implications. (2023). Bleeding, Thrombosis and Vascular Biology, 2(2). https://doi.org/10.4081/btvb.2023.66
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