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Cellular and Molecular Life Sciences

, Volume 76, Issue 16, pp 3083–3095 | Cite as

Matrix metalloproteinases in the CNS: interferons get nervous

  • Sameeksha Chopra
  • Christopher M. Overall
  • Antoine DufourEmail author
Review

Abstract

Matrix metalloproteinases (MMPs) have been investigated in context of chronic inflammatory diseases and demonstrated to degrade multiple components of the extracellular matrix (ECM). However, following several disappointing MMP clinical trials, recent studies have demonstrated unexpected novel functions of MMPs in viral infections and autoimmune inflammatory diseases in unanticipated locations. Thus, MMPs play additional functions in inflammation than just ECM degradation. They can regulate the activity of chemokines and cytokines of the immune response by precise proteolytic processing resulting in activation or inactivation of signaling pathways. MMPs have been demonstrated to cleave multiple substrates of the central nervous systems (CNS) and contribute to promoting and dampening diseases of the CNS. Initially, believed to be solely promoting pathologies, more than 10 MMPs to date have been shown to have protective functions. Here, we present some of the beneficial and destructive roles of MMPs in CNS pathologies and discuss strategies for the use of MMP inhibitors.

Keywords

Matrix metalloproteinase (MMP) Interferon (IFN) Inflammation Extracellular matrix (ECM) Virus Multiple sclerosis (MS) 

Abbreviations

AIDS

Acquired immunodeficiency syndrome

BBB

Blood brain barrier

CNS

Central nervous system

CVB3

Coxsackievirus type B3

ECM

Extracellular matrix

ECs

Ependymal cells

HIV

Human immunodeficiency virus

IFN

Interferon

MBP

Myelin basic protein

MMP

Matrix metalloproteinase

MS

Multiple Sclerosis

RSV

Respiratory syncytial virus

SLE

Systemic lupus erythematosus

SLEDAI

Systemic lupus erythematosus disease activity index

TIMP

Tissue inhibitor of metalloprotease

Notes

Acknowledgements

We thank Dr. V. Wee Yong, University of Calgary, AB for the help supervising Chopra’s project related to this review. C.M.O holds a Canada Research Chair in Protease Proteomics and Systems Biology. This work was supported by the Southern Alberta Mass Spectrometry (SAMS) Facility, University of Calgary and McCaig Institute and by the Canadian Institutes of Health Research Grants (MOP-37937 to C.M.O.).

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Physiology and Pharmacology, Cumming School of MedicineUniversity of CalgaryCalgaryCanada
  2. 2.McCaig Institute for Bone and Joint HealthUniversity of CalgaryCalgaryCanada
  3. 3.Department of Oral Biological and Medical Sciences, Faculty of DentistryUniversity of British ColumbiaVancouverCanada
  4. 4.Centre for Blood ResearchVancouverCanada

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