The inflammatory APRIL (a proliferation-inducing ligand) antagonizes chondroitin sulphate proteoglycans to promote axonal growth and myelination
Year: 2024
Type: article
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.
Source: Brain Communications
Institutions: Centre National de la Recherche Scientifique, Inserm, Institut pour l'avancée des biosciences, Université Grenoble Alpes, Translational Innovation in Medicine and Complexity, Grenoble Institute of Neurosciences, Health and Functional Exposomics, University Hospital Münster, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut de Biologie Structurale, Ollscoil na Gaillimhe – University of Galway, University of Lausanne
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,095
OpenAlex ID: W4407348586