PMID- 12910628
OWN - NLM
STAT- MEDLINE
DCOM- 20031023
LR  - 20061115
IS  - 1295-0661 (Print)
IS  - 1295-0661 (Linking)
VI  - 197
IP  - 2
DP  - 2003
TI  - [Matrix metalloproteinases and their inhibitors, modulators of neuro-immune 
      interactions and of pathophysiological processes in the nervous system].
PG  - 133-44
AB  - The matrix metalloproteinases (MMPs) belong to a growing family of Zn2+-dependent 
      endopeptidases, secreted or membrane-bound (MT-MMP), that regulate or degrade by 
      proteolytic cleavage protein components of the extracellular matrix, cytokines, 
      chemokines, cell adhesion molecules and a variety of membrane receptors. MMP 
      activity is counterbalanced by their physiological inhibitors, the tissue 
      inhibitors of MMPs (TIMPs), a family of 4 secreted multifunctional proteins that 
      have growth promoting activities. In physiological conditions MMP activity is 
      tightly regulated and altered MMP regulation is associated with pathological 
      processes including inflammation, cell proliferation, cell death and tissue 
      remodeling. The MMP/TIMP system is involved in the development and function of 
      cells of the immune system by promoting their differentiation, activation, 
      migration across basement membranes and tissues. In the last years, data has 
      accumulated indicating that the MMP/TIMP system is expressed in the nervous 
      system where it regulates neuro-immune interactions and plays a major role in 
      pathophysiological processes. In this review, we present recent in vivo and in 
      vitro studies that highlight the contribution of the MMP/TIMP system to various 
      diseases of the nervous system, involving blood brain barrier breakdown, 
      neuroinflammation, glial reactivity, neuronal death, reactive plasticity, and to 
      developmental and physiological processes including cell migration, axonal 
      sprouting and neuronal plasticity. This review also alludes to the beneficial 
      effects of synthetic MMP inhibitors in different animal models of neuropathology. 
      In all, a further understanding of the role of MMPs and TIMPs in the nervous 
      system should contribute to unravel mechanisms of neuronal plasticity and 
      pathology and set the basis of new therapeutic strategies in nervous system 
      disorders based on the development of synthetic MMP inhibitors.
FAU - Khrestchatisky, Michel
AU  - Khrestchatisky M
AD  - FRE CNRS 2533, Universite de la Mediterranee, Faculte de Medecine, IFR Jean 
      Roche, 27 Bd Jean Moulin, 13385 Marseille. 
      khrestchatisky.m@jean-roche.univ-mrs.fr
FAU - Jourquin, Jerome
AU  - Jourquin J
FAU - Ogier, Crystel
AU  - Ogier C
FAU - Charton, Gerard
AU  - Charton G
FAU - Bernard, Anne
AU  - Bernard A
FAU - Tremblay, Evelyne
AU  - Tremblay E
FAU - Rivera, Santiago
AU  - Rivera S
LA  - fre
PT  - English Abstract
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
TT  - Les Metalloproteases de la matrice et leurs inhibiteurs, des modulateurs des 
      interactions neuro-immunes et des processus physiopathologiques dans le systeme 
      nerveux.
PL  - France
TA  - J Soc Biol
JT  - Journal de la Societe de biologie
JID - 100890617
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - EC 3.4.24.- (Metalloendopeptidases)
SB  - IM
MH  - Animals
MH  - Blood-Brain Barrier/physiology
MH  - Disease Models, Animal
MH  - Humans
MH  - Metalloendopeptidases/*metabolism
MH  - Nervous System Diseases/enzymology/*immunology/*physiopathology
MH  - Tissue Inhibitor of Metalloproteinases/*metabolism
RF  - 69
EDAT- 2003/08/13 05:00
MHDA- 2003/10/24 05:00
CRDT- 2003/08/13 05:00
PHST- 2003/08/13 05:00 [pubmed]
PHST- 2003/10/24 05:00 [medline]
PHST- 2003/08/13 05:00 [entrez]
PST - ppublish
SO  - J Soc Biol. 2003;197(2):133-44.