Multifaceted role of matrix metalloproteinases (MMPs).

Divya Singh,Tapas K Chaudhuri,Sanjeev K Srivastava,Ghanshyam Upadhyay

doi:10.3389/fmolb.2015.00019

Abstract

Matrix metalloproteinases (MMPs), a large family of calcium-dependent zinc-containing endopeptidases, are involved in the tissue remodeling and degradation of the extracellular matrix. MMPs are widely distributed in the brain and regulate various processes including microglial activation, inflammation, dopaminergic apoptosis, blood-brain barrier disruption, and modulation of α-synuclein pathology. High expression of MMPs is well documented in various neurological disorders including Parkinson's disease (PD), Alzheimer's disease (AD), Japanese encephalitis (JE), and Glaucoma. Although potentially critical, the role of MMPs in neuronal disorders is under-investigated. The present review summarizes the role of MMPs in neurodegeneration with a particular emphasis on PD, AD, JE, and Glaucoma.

Highlights

Matrix metalloproteinases (MMPs) are described as calcium-dependent zinc endopeptidases
Growing body of knowledge suggests the dual role of MMPs in Alzheimer’s disease (AD) pathogenesis. At one hand it directly degrade amyloid-β peptides (Aβ) resulting in reduction in Aβ deposit (Yan et al, 2006; Miners et al, 2008); again, these could contribute to brain parenchymal destruction when induced by Aβ in microglia, astrocytes or vascular smooth muscle cells
Shukla et al demonstrated higher concentrations of MMP-2, TIMP-2, and TIMP-3 in cerebrospinal fluid (CSF) and serum of children with JE virus (JEV) as compared with disease control (DC) (Shukla et al, 2013). They observed a higher concentration of MMP-9 and MMP-7 in the serum of JEV patients when compared with DC and healthy control but not in CSF (Shukla et al, 2013)

Summary

Introduction

Matrix metalloproteinases (MMPs) are described as calcium-dependent zinc endopeptidases. The roles of MMPs have been demonstrated in extracellular matrix (ECM) degradation and remodeling of tissues. MMPs act on the different segments of ECM like collagen, gelatin, and elastin. MMPs are classified into four primary subgroups on the premise of domain structure: collagenases, gelatinases, stromelysins, and film sort (MT)-MMPs. Collagenases degrade triple helical fibrillary collagens, which are the fundamental segments of bone and ligament. Stromelysins (MMP-3, MMP-10, MMP-11, and MMP-7) are small proteases that degrade segments of the extracellular matrix. The role of MMPs in neuronal disorders is underinvestigated. In this brief review, we have made an attempt to shed a light on the role of MMPs in neurological disorders with a particular emphasis on Parkinson’s disease, Alzheimer’s disease, Glaucoma, and Japanese encephalitis

MMPs in Nervous System

Role of MMPs in Japanese Encephalitis

Role of MMPs in Glaucoma

Conclusion