The extracellular matrix (ECM) is a major regulator of cellular behaviour in the central nervous system (CNS), influencing neural plasticity, repair, and disease progression. Historically, CNS ECM research has been dominated by efforts to overcome its inhibitory properties, particularly following spinal cord injury, where matrix components were viewed largely as barriers to regeneration. Similar approaches have emerged in neurodegenerative diseases, where perineuronal nets (PNNs), specialised ECM structures that surround subsets of neurons, are often targeted for removal to restore plasticity.

However, growing evidence suggests that the CNS matrix is far more than a passive obstacle. Rather than acting as a uniform regulator, the ECM contains molecular information that can direct distinct cellular responses. Variations in glycosaminoglycan sulfation patterns, particularly the balance between 4-sulfated and 6-sulfated chondroitin sulfate motifs, can profoundly influence neuronal plasticity, memory processes, and the functional properties of PNNs. Emerging findings further indicate that glial cells are also sensitive to these matrix signals, highlighting complex and dynamic interactions between the ECM and multiple CNS cell types.

In this presentation, I shall provide an overview of how our understanding of the CNS extracellular matrix has evolved from a focus on matrix removal towards an appreciation of its instructive and information-rich functions. Drawing on work spanning spinal cord injury, memory, ageing, and neurodegeneration, the talk will explore how matrix composition and organization shape cellular behaviour and discuss the implications of these insights for future therapeutic strategies.

More information:

• https://biologicalsciences.leeds.ac.uk/school-biomedical-sciences/staff/99/dr-jessica-c-f-kwok