Molecular Neurobiology

, Volume 19, Issue 3, pp 267–284 | Cite as

Extracellular matrix degradation by metalloproteinases and central nervous system diseases

  • Anton LukesEmail author
  • Sheila Mun-Bryce
  • Manuela Lukes
  • Gary A. Rosenberg


Matrix metalloproteinases (MMPs) are a gene family of neutral proteases involved in normal and pathological processes in the central nervous system (CNS). Normally released into the extracellular space, MMPs break down the extracellular matrix (ECM) to allow cell growth and to facilitate remodeling. Proteolysis becomes pathological when the normal balance between the proteases and their inhibitors, tissue inhibitors to metalloproteinases (TIMPs), is lost. Cancer cells secrete neutral proteases to facilitate spread through the ECM. MMPs increase capillary permeability, and they have been implicated in demyelination. Neurological diseases, such as brain tumors, multiple sclerosis, Guillain-Barré, ischemia, Alzheimer's disease, and infections, lead to an increase in the matrix-degrading proteases. Two classes of neutral proteases have been extensively studied, namely the MMPs and the plasminogen activators (PAs), which act in concert to attack the ECM. After proteolytic injury occurs, the process of ECM remodeling begins, which can lead to fibrosis of blood vessels and gliosis. TIMPs are increased after the acute injury and may add to the fibrotic buildup of ECM components. Thus, an inbalance in proteolytic activity either during the acute injury or in recovery may aggravate the underlying disease process. Agents that affect the proteolytic process at any of the regulating sites are potentially useful in therapy.

Index Entries

Blood-brain barrier brain tumors cerebral ischemia extracellular matrix matrix metalloproteinases 


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Copyright information

© Humana Press Inc 1999

Authors and Affiliations

  • Anton Lukes
    • 1
    Email author
  • Sheila Mun-Bryce
    • 1
  • Manuela Lukes
    • 1
  • Gary A. Rosenberg
    • 1
    • 2
    • 3
  1. 1.The Department of NeurologyUniversity of New Mexico School of MedicineAlbuquerque
  2. 2.The Department of Cell Biology and PhysiologyUniversity of New Mexico School of MedicineAlbuquerque
  3. 3.The Department of NeuroscienceUniversity of New Mexico School of MedicineAlbuquerque

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