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Cellular and Molecular Life Sciences

, Volume 76, Issue 16, pp 3229–3248 | Cite as

Demystifying the extracellular matrix and its proteolytic remodeling in the brain: structural and functional insights

  • Venkat Raghavan Krishnaswamy
  • Amit Benbenishty
  • Pablo Blinder
  • Irit SagiEmail author
Review

Abstract

The extracellular matrix (ECM) plays diverse roles in several physiological and pathological conditions. In the brain, the ECM is unique both in its composition and in functions. Furthermore, almost all the cells in the central nervous system contribute to different aspects of this intricate structure. Brain ECM, enriched with proteoglycans and other small proteins, aggregate into distinct structures around neurons and oligodendrocytes. These special structures have cardinal functions in the normal functioning of the brain, such as learning, memory, and synapse regulation. In this review, we have compiled the current knowledge about the structure and function of important ECM molecules in the brain and their proteolytic remodeling by matrix metalloproteinases and other enzymes, highlighting the special structures they form. In particular, the proteoglycans in brain ECM, which are essential for several vital functions, are emphasized in detail.

Keywords

Brain Extracellular matrix Matrix remodeling Nodes of Ranvier Perineuronal nets Proteases Synapses 

Abbreviations

AMPAR

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor

AP-1

Activator protein 1

ASD

Autism spectrum disorders

Bral

Brain-specific hyaluronan-binding protein

CAM

Cell adhesion molecule

Cbln

Cerebellin

CNS

Central nervous system

CREB

cAMP-response element-binding

CRP

Complement regulatory protein

CSPG

Chondroitin sulfate proteoglycan

DCC

Deleted in colorectal cancer

ECD

Extracellular domain

ECM

Extracellular matrix

GAG

Glycosaminoglycan

HA

Hyaluronic acid

HAPLN1

Hyaluronan and proteoglycan link protein 1

HAS

Hyaluronan synthase

HSPG

Heparin sulfate proteoglycan

LTD

Long-term depression

LTP

Long-term potentiation

L-VDCC

l-type voltage-dependent Ca2+ channels

MMP

Matrix metalloproteinase

NMDAR

N-methyl-d-aspartate receptor

Narp

Neuronal activity-regulated pentraxin

NF-186

Neurofascin-186

NGC

Neuroglycan C

NrCAM

Neuron–glia-related cell adhesion molecule

PNN

Perineuronal net

PSI

Phosphacan short isoform

PTR

Proteoglycan tandem repeat

RPTP

Receptor-type protein-tyrosine phosphatase

SGGL

Sulfoglucuronyl glycolipid

SNAP-25

Synaptosomal nerve-associated protein 25

TIMP

Tissue inhibitor of MMPs

TNC

Tenascin-C

TNR

Tenascin-R

tPA

Tissue plasminogen activator

Notes

Acknowledgements

Irit Sagi is an Incumbent of the Maurizio Pontecorvo Professorial Chair and has received funding from the Israeli Science Foundation (1226/13), the European Research Council AdG (THZCALORIMETRY—DLV-695437), and the USA-Israel Binational Science Foundation (712506-01). She is grateful for the Azrieli Foundation for its generous grant to conduct research on the extracellular matrix of the brain.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Venkat Raghavan Krishnaswamy
    • 1
  • Amit Benbenishty
    • 1
  • Pablo Blinder
    • 2
    • 3
  • Irit Sagi
    • 1
    Email author
  1. 1.Department of Biological RegulationWeizmann Institute of ScienceRehovotIsrael
  2. 2.Neurobiology, Biochemistry and Biophysics SchoolTel Aviv UniversityTel AvivIsrael
  3. 3.Sagol School for NeuroscienceTel Aviv UniversityTel AvivIsrael

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