The inflammatory APRIL (a proliferation-inducing ligand) antagonizes chondroitin sulphate proteoglycans to promote axonal growth and myelination.

IF 4.1 Q1 CLINICAL NEUROLOGY Brain communications Pub Date : 2025-02-07 eCollection Date: 2025-01-01 DOI:10.1093/braincomms/fcae473

Mashal Claude Ahmed, Tejaswini Kakunuri, Leticia Peris, Delphine Meffre, Elif Nur Yilmaz, Laureen Grewing, Raquel Guerrero González, Benoit Manfroi, Evelyne Gout, Romain R Vivès, Una Fitzgerald, Pascal Schneider, Mehrnaz Jafarian-Tehrani, Tanja Kuhlmann, Bertrand Huard

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Abstract

Lesions in the CNS are frequently associated to a detrimental inflammatory reaction. In autoimmune neurodegenerative diseases, a proliferation-inducing ligand (APRIL) produced by CNS-infiltrating inflammatory cells binds to chondroitin sulphate proteoglycans (CSPGs). The latter are well-established obstacles to neural regeneration and remyelination in the CNS by interacting with receptor protein tyrosine phosphatase (RPTP) and Nogo receptor (NgR) families. Here, we are showing that APRIL blocks the interactions of RPTP and NgR with all types of chondroitin sulphate (CS). Functionally, APRIL neutralized the inhibitory effects of CS on mouse and human neuronal process growth. APRIL also blocked the inhibition of CS on mouse and human oligodendrocyte differentiation. Finally, APRIL increased myelination in an ex vivo organotypic model of demyelination in the presence of endogenous CSPG upregulation. Our data demonstrate the potential value for a recombinant form of soluble APRIL to achieve repair in the CNS.

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