Abstract

Background: Matrix metalloproteinases (MMPs) are pleiotropic enzymes involved in extracellular protein degradation and turnover. MMPs are implicated in the pathogenesis of many neurological diseases, including multiple sclerosis (MS).Objective: To search the level of MMPs in the cerebrospinal fluid (CSF) of MS patients and detect possible disease-specific patterns.Methods: CSF samples from 32 MS patients and, from 15 control subjects with other inflammatory neurological diseases (OIND) were analyzed. The Bio-Plex Pro Human MMP 9-Plex Panel (Bio-Rad) was used for the quantification of MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-12, and MMP-13.Results: CSF MMP-1 and MMP-12 levels were significantly reduced in MS as compared with OIND. In MS patients' CSF: (i) MMP-1 levels were significantly higher in women vs. men; (ii) MMP-10 concentrations were higher in patients with CSF-restricted IgG oligoclonal bands, and (iii) MMP-7 levels were increased in patients with longer disease duration. In the OIND group MMP-7 and MMP-12 levels significantly and directly correlated with age.Conclusions: Our study contributes to investigating the role of MMPs in MS, with regard to CSF immunological features and disease duration. Sex-specific differences were also detected in MMPs CSF levels.

Highlights

  • In multiple sclerosis (MS) the migration of immunocompetent cells into the central nervous system (CNS) requires the opening of the blood-brain barrier (BBB) [1], a mechanism in which proteins degradation represents a crucial step [2]

  • The study was conducted on 47 individuals, 32 patients with a diagnosis of MS, and 15 control subjects suffering from other inflammatory neurological diseases (OIND)

  • The women:men ratio was marginally higher in the MS than in the OIND group (3:1 vs. 0.9:1; p = 0.056), and mean age at study time was significantly higher in the OIND than in the MS group (58.6 vs. 39.4 years, p = 0.000004)

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Summary

Introduction

In multiple sclerosis (MS) the migration of immunocompetent cells into the central nervous system (CNS) requires the opening of the blood-brain barrier (BBB) [1], a mechanism in which proteins degradation represents a crucial step [2]. Matrix metalloproteinases (MMPs) are pleiotropic calcium-requiring and zinc-containing proteolytic enzymes involved in extracellular matrix (ECM) degradation and turnover [3]. MMPs are members of the metzincins family, so named for the Matrix Metalloproteinases in Cerebrospinal Fluid presence of a conserved Methionine residue at the active site and for the use of a zinc ion in the enzymatic reaction [4]. Matrix metalloproteinases (MMPs) are pleiotropic enzymes involved in extracellular protein degradation and turnover. MMPs are implicated in the pathogenesis of many neurological diseases, including multiple sclerosis (MS)

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