Matrix metalloproteinase-9 (MMP-9): A macromolecular mediator in CNS infections: A review

Abstract

Matrix metalloproteinase-9 (MMP-9) is a macromolecular zinc-dependent endopeptidase that plays a critical role in the pathogenesis of Central Nervous System (CNS) infections by modulating extracellular matrix remodelling and blood-brain barrier (BBB) dynamics. This review elucidates the structural and functional properties of MMP-9, highlighting its distinct domain architecture that enables substrate specificity and regulatory mechanisms. MMP-9-mediated BBB disruption is a hallmark of bacterial, viral, fungal, and parasitic CNS infections, facilitating immune cell infiltration and pathogen entry while exacerbating neuroinflammation and tissue damage. Elevated MMP-9 levels in cerebrospinal fluid (CSF) correlate with disease severity, suggesting its potential as a diagnostic biomarker. Advances in therapeutic strategies targeting MMP-9, including small molecule inhibitors, monoclonal antibodies, and peptide-based therapies, demonstrate promising results in mitigating BBB disruption and neuroinflammation. This comprehensive review underscores the dual role of MMP-9 as both a biomarker and therapeutic target, advocating for its inclusion in adjunctive treatment regimens to improve outcomes in CNS infections. Future research should focus on refining MMP-9 inhibitors for clinical use, ensuring specificity, and minimizing off-target effects to harness its full therapeutic potential.