ArticleNature communications2023
Small leucine-rich proteoglycans inhibit CNS regeneration by modifying the structural and mechanical properties of the lesion environment.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Purinergic Receptor P2Y2 Regulates Neurogenesis and Functional Recovery Following Spinal Cord Injury in Zebrafish.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
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- Keratan Sulfate: An Electroconductive Glycosaminoglycan at the Interface of Sensory Perception and Neural Signaling.Journal of neuroscience research · 2026Review
- Extracellular matrix remodelling in neurological diseases.Nature reviews. Neurology · 2026Review
- The microglia-derived protein Sema4ab attenuates regenerative neurogenesis after spinal cord injury in zebrafish.PLoS biology · 2026Article
- Proteomic Signatures of Regeneration: Uncovering Extracellular Matrix-Associated Cues in Goldfish Spinal Cord Repair.The Journal of comparative neurology · 2026Article
- Article
- Hyaluronic acid and tissue mechanics orchestrate mammalian digit tip regeneration.Science (New York, N.Y.) · 2026Article
- Signal control during tissue regeneration in adult animals.Nature reviews. Molecular cell biology · 2026Review
- Time-dependent adaptations of damaged neurons and their microenvironment in the regenerating adult zebrafish spinal cord.Science advances · 2026Article
- Mouse digit AAV gene delivery into fibroblasts regulates regenerative outcome.Science advances · 2026Article
- Mechanisms underpinning spontaneous spinal cord regeneration.Development (Cambridge, England) · 2025Review
- From Biophysics to Biomedical Physics.ACS bio & med chem Au · 2025Review
- Blueprints for healing: central nervous system regeneration in zebrafish and neonatal mice.BMC biology · 2025Review
- Fecal microbiota transplantation promotes functional recovery in mice with spinal cord injury by modulating the spinal cord microenvironment.Journal of translational medicine · 2025Article
- Correction: Microglia are essential for tissue contraction in wound closure after brain injury in zebrafish larvae.Life science alliance · 2025Article
- Microglia are essential for tissue contraction in wound closure after brain injury in zebrafish larvae.Life science alliance · 2025Article
- Dual role of complement in neuronal repair.Frontiers in immunology · 2025Review
- Astrocytic and microglial cell functions in neuroinflammatory diseases and their animal models.Frontiers in cellular neuroscience · 2025Review
- Single-cell analysis of innate spinal cord regeneration identifies intersecting modes of neuronal repair.Nature communications · 2024Article
Corrections and comments
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Authors and funding
27 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extracellular matrix (ECM) deposition after central nervous system (CNS) injury leads to inhibitory scarring in humans and other mammals, whereas it facilitates axon regeneration in the zebrafish. However, the molecular basis of these different fates is not understood. Here, we identify small leucine-rich proteoglycans (SLRPs) as a contributing factor to regeneration failure in mammals. We demonstrate that the SLRPs chondroadherin, fibromodulin, lumican, and prolargin are enriched in rodent and human but not zebrafish CNS lesions. Targeting SLRPs to the zebrafish injury ECM inhibits axon regeneration and functional recovery. Mechanistically, we find that SLRPs confer mechano-structural properties to the lesion environment that are adverse to axon growth. Our study reveals SLRPs as inhibitory ECM factors that impair axon regeneration by modifying tissue mechanics and structure, and identifies their enrichment as a feature of human brain and spinal cord lesions. These findings imply that SLRPs may be targets for therapeutic strategies to promote CNS regeneration.
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