PMID- 11433375
OWN - NLM
STAT- MEDLINE
DCOM- 20010802
LR  - 20240328
IS  - 1471-003X (Print)
IS  - 1471-0048 (Electronic)
IS  - 1471-003X (Linking)
VI  - 2
IP  - 7
DP  - 2001 Jul
TI  - Metalloproteinases in biology and pathology of the nervous system.
PG  - 502-11
AB  - Matrix metalloproteinases (MMPs) have been implicated in several diseases of the 
      nervous system. Here we review the evidence that supports this idea and discuss 
      the possible mechanisms of MMP action. We then consider some of the beneficial 
      functions of MMPs during neural development and speculate on their roles in 
      repair after brain injury. We also introduce a family of proteins known as ADAMs 
      (a disintegrin and metalloproteinase), as some of the properties previously 
      ascribed to MMPs are possibly the result of ADAM activity.
FAU - Yong, V W
AU  - Yong VW
AD  - Department of Oncology, University of Calgary, 3330 Hospital Drive, Calgary, 
      Alberta, Canada T3A 2Z1. vyong@ucalgary.ca
FAU - Power, C
AU  - Power C
FAU - Forsyth, P
AU  - Forsyth P
FAU - Edwards, D R
AU  - Edwards DR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Nat Rev Neurosci
JT  - Nature reviews. Neuroscience
JID - 100962781
RN  - 0 (Disintegrins)
RN  - EC 3.4.24.- (Metalloendopeptidases)
SB  - IM
MH  - Alzheimer Disease/enzymology
MH  - Animals
MH  - Axons/enzymology
MH  - Central Nervous System/enzymology/growth & development
MH  - Central Nervous System Viral Diseases/enzymology
MH  - Disintegrins/*metabolism
MH  - Enzyme Activation/physiology
MH  - Glioma/enzymology
MH  - Humans
MH  - Metalloendopeptidases/*metabolism
MH  - Neoplasm Invasiveness
MH  - Nervous System Diseases/*enzymology
MH  - Protein Structure, Tertiary/physiology
MH  - Stroke/enzymology
PMC - PMC7097548
OAB - Matrix metalloproteinases (MMPs) and ADAMs (a disintegrin and metalloproteinase) 
      are part of a larger family of structurally related zinc-dependent 
      metalloproteinases called metzincins. Structurally, MMPs are divided in three 
      domains: an amino-terminal propeptide region, an amino-terminal catalytic domain, 
      and a carboxy-terminal domain that is involved in substrate binding. ADAMs have a 
      prodomain, a metalloprotease region, a disintegrin domain for adhesion, a 
      cysteine-rich region, epidermal-growth-factor repeats, a transmembrane module and 
      a cytoplasmic tail. . The activity of MMPs is tightly regulated in several ways: 
      at the level of transcription, by post-translational modifications such as 
      proteolysis, and through the action of endogenous tissue inhibitors of 
      metalloproteinases. The regulation of ADAMs is less well understood, although 
      there is some evidence that the same three levels of regulation might control 
      ADAM activity. . MMPs and ADAMs have been implicated in neuroinflammation and 
      multiple sclerosis (MS), in the pathogenesis of malignant gliomas, and in other 
      neurological conditions such as stroke, viral infections and Alzheimer's disease. 
      In the case of ADAMs, their role in these pathological states has begun to be 
      explored, but the available literature is still in its infancy. . Although the 
      detrimental roles of metalloproteinases are well documented, some of their 
      functions in the central nervous system (CNS) might be beneficial. For example, 
      some metalloproteinases are expressed in the CNS during development, pointing to 
      a possible role in brain maturation. Similarly, metalloproteinases have been 
      implicated in myelinogenesis and axon growth. Furthermore, metalloproteinases are 
      upregulated after injury to the CNS, indicating a possible relevance to tissue 
      repair. . Several challenges remain in the study of metalloproteinases and their 
      role in brain function. It will be necessary to understand the balance between 
      the beneficial and detrimental roles of MMPs to determine whether they can be 
      used as targets for therapeutic intervention. It will also be important to 
      identify the physiological substrates of the different metalloproteinases, and to 
      develop selective antagonists against the various members of the 
      metalloproteinase families; the lack of such tools constitutes one of the main 
      limitations to the growth of the field at present. .
OABL- eng
EDAT- 2001/07/04 10:00
MHDA- 2001/08/03 10:01
PMCR- 2020/03/26
CRDT- 2001/07/04 10:00
PHST- 2001/07/04 10:00 [pubmed]
PHST- 2001/08/03 10:01 [medline]
PHST- 2001/07/04 10:00 [entrez]
PHST- 2020/03/26 00:00 [pmc-release]
AID - 35081571 [pii]
AID - BF35081571 [pii]
AID - 10.1038/35081571 [doi]
PST - ppublish
SO  - Nat Rev Neurosci. 2001 Jul;2(7):502-11. doi: 10.1038/35081571.