Mini-reviews
3 May 2023
Vol. 2 No. 2 (2023)
https://doi.org/10.4081/btvb.2023.66

Tumor necrosis factor superfamily in multiple sclerosis: from pathology to therapeutic implications

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TNF, multiple sclerosis, synaptopathy, TNFR1, TNFR2
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Authors

Federica Azzolini
Unit of Neurology, IRCCS Neuromed, Pozzilli, Italy.
Antonio Bruno
Unit of Neurology, IRCCS Neuromed, Pozzilli, Italy.
Ettore Dolcetti
Unit of Neurology, IRCCS Neuromed, Pozzilli, Italy.
Diego Centonze
centonze@uniroma2.it
Unit of Neurology, IRCCS Neuromed, Pozzilli, Italy; Synaptic Immunopathology Lab, Department of Systems Medicine, Tor Vergata University, Rome, Italy.
Fabio Buttari
Synaptic Immunopathology Lab, Department of Systems Medicine, Tor Vergata University, Rome, Italy.

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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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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