The Significance of Matrix Metalloproteinases in Parasitic Infections Involving the Central Nervous System.

Matrix metalloproteinases (MMPs) represent a large family of over twenty different secreted or membrane-bound endopeptidases, involved in many physiological (embryogenesis, precursor or stem cell mobilization, tissue remodelingduring wound healing, etc.), as well aspathological (inflammation, tumor progression and metastasis in cancer, vascular pathology, etc.) conditions. For a long time, MMPs were considered only for the ability to degrade extracellular matrix (ECM) molecules (e.g.,collagen, laminin, fibronectin) and to release hidden epitopes fromthe ECM. In the last few years, it has been fully elucidated that these molecules have many other functions, mainly related to the immune response, in consideration of their effects on cytokines, hormones and chemokines. Among others, MMP-2 and MMP-9 are endopeptidases of the MMP family produced by neutrophils, macrophages and monocytes. When infection is associated with leukocyte influx into specific organs, immunopathology and collateral tissue damage may occur.In this review, the involvement of MMPs and,in particular,of gelatinases in both protozoan and helminth infections will be described. Incerebral malaria, for example, MMPs play a role in the pathogenesis of such diseases.Also,trypanosomosis and toxoplasmosis will be considered for protozoan infections,as well asneurocysticercosis and angiostrongyloidosis, as regards helminthiases.All these situations have in common the proteolytic actionontheblood brain barrier, mediated by MMPs.