PMID- 17387691
OWN - NLM
STAT- MEDLINE
DCOM- 20080117
LR  - 20220310
IS  - 0360-4012 (Print)
IS  - 0360-4012 (Linking)
VI  - 85
IP  - 13
DP  - 2007 Oct
TI  - Matrix metalloproteinases in brain development and remodeling: synaptic functions 
      and targets.
PG  - 2813-23
AB  - Matrix metalloproteinases (MMPs) play critical roles in egg fertilization, 
      embryonic development, wound repair, cancer, and inflammatory and neurologic 
      diseases. This subfamily of metzincin peptidases can cleave extracellular matrix 
      (ECM) and pericellular proteins that have profound effects on cell behavior. 
      Among known MMP substrates are several proteins that play important roles in 
      synaptogenesis, synaptic plasticity, and long-term potentiation (LTP). In this 
      Mini-Review we discuss how MMP-directed cleavage of these proteins can impact the 
      formation and function of synapses within the brain. Pyramidal neurons in the 
      hippocampus, and other large neurons, are surrounded by perineuronal nets that 
      are composed of brevican, tenascin-R, and laminin, each of which is subject to 
      proteolytic cleavage by MMPs. Tenascin-R knockout mice show deficits in learning 
      and memory and LTP, as do at least two MMP knockouts. Impaired LTP is also seen 
      in brain-derived neurotrophic factor (BDNF) knockout mice, which is interesting 
      in that pro-BDNF can be processed into mature BDNF by several MMPs and thereby 
      regulate activation of the high-affinity BDNF receptor TrkB. At the synaptic 
      level, MMP substrates also include ephrins, Eph receptors, and cadherins, which 
      are also involved in synapse development and plasticity. MMPs can also process 
      membrane-bound tumor necrosis factor-alpha into a potent soluble cytokine that is 
      increasingly implicated in neuron-glial signaling, particularly in neurologic 
      disease. Finally, we discuss how the development of therapeutics to attenuate MMP 
      activity in neurodegenerative disorders may become powerful tools for future 
      studies of synaptic formation and function within the developing and mature 
      brain.
CI  - 2007 Wiley-Liss, Inc.
FAU - Ethell, Iryna M
AU  - Ethell IM
AD  - Division of Biomedical Sciences, University of California Riverside, Riverside, 
      California 92521-0121, USA. iryna.ethell@ucr.edu
FAU - Ethell, Douglas W
AU  - Ethell DW
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Animals
MH  - Brain/*enzymology/*growth & development
MH  - Matrix Metalloproteinases/*metabolism
MH  - Models, Neurological
MH  - Neuronal Plasticity/*physiology
MH  - Synapses/*physiology
RF  - 91
EDAT- 2007/03/28 09:00
MHDA- 2008/01/18 09:00
CRDT- 2007/03/28 09:00
PHST- 2007/03/28 09:00 [pubmed]
PHST- 2008/01/18 09:00 [medline]
PHST- 2007/03/28 09:00 [entrez]
AID - 10.1002/jnr.21273 [doi]
PST - ppublish
SO  - J Neurosci Res. 2007 Oct;85(13):2813-23. doi: 10.1002/jnr.21273.