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Related Concept Videos

Multiple Sclerosis l: Introduction01:19

Multiple Sclerosis l: Introduction

Multiple sclerosis is a chronic autoimmune disease of the central nervous system (CNS) that affects the brain, spinal cord, and optic nerves. It is an inflammatory demyelinating disorder and a leading cause of neurological disability in young adults.EpidemiologyMS commonly begins between 20 and 40 years of age and is twice as common in women. Its exact cause remains unclear, but genetic susceptibility contributes, with higher risk in first-degree relatives and identical twins. A greater...
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Unlike epithelial tissue, which is composed of cells closely packed with little or no extracellular space in between, connective tissue cells are dispersed in a matrix. This extracellular matrix (ECM) is composed of fibrous proteins like collagen, elastin, and fibronectin in a ground substance consisting of interstitial fluid, cell adhesion proteins, and proteoglycans. The proteoglycans form a gel-like material in the spaces between cells and provide hydration, buffering, binding, and force...
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In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
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Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
09:41

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Published on: July 19, 2019

Extensive extracellular matrix depositions in active multiple sclerosis lesions.

Jack van Horssen1, Lars Bö, Christien D Dijkstra

  • 1Department of Molecular Cell Biology and Immunology, VU University Medical Center Amsterdam, PO Box 7057, 1007 MB Amsterdam, The Netherlands. j.vanhorssen@vumc.nl

Neurobiology of Disease
|September 29, 2006
PubMed
Summary

Multiple sclerosis lesions show altered basement membrane (BM) proteins forming parenchymal networks. These networks, associated with TGF-beta1 and macrophages, may impede axonal regeneration.

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Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Basement membrane (BM) components are typically linked to CNS vasculature.
  • Inflammation can alter BM component expression in the central nervous system.

Purpose of the Study:

  • To investigate the distribution of BM components (laminin, collagen IV, heparan sulfate proteoglycans) in multiple sclerosis (MS) lesions.
  • To explore the association of transforming growth factor-beta1 (TGF-beta1) with these altered BM structures.

Main Methods:

  • Immunohistochemical analysis of MS lesions (active and chronic inactive) and control brains.
  • Detection of laminin, collagen type IV, heparan sulfate proteoglycans, TGF-beta1, CD68-positive macrophages.

Main Results:

  • Irregular and discontinuous BMs observed in active MS lesions.
  • Dense, parenchymal networks of BM proteins found in active MS lesions, independent of vasculature.
  • These parenchymal BM networks were absent in chronic inactive lesions and controls.
  • TGF-beta1 was highly expressed by macrophages near parenchymal BM deposits.

Conclusions:

  • Altered BM composition and deposition occur in active MS lesions.
  • Parenchymal BM networks may contribute to inflammatory cell recruitment.
  • These networks could potentially hinder axonal regeneration in MS.