PMID- 31172218
OWN - NLM
STAT- MEDLINE
DCOM- 20190729
LR  - 20200325
IS  - 1420-9071 (Electronic)
IS  - 1420-682X (Print)
IS  - 1420-682X (Linking)
VI  - 76
IP  - 16
DP  - 2019 Aug
TI  - MMPs and ADAMs in neurological infectious diseases and multiple sclerosis.
PG  - 3097-3116
LID - 10.1007/s00018-019-03174-6 [doi]
AB  - Metalloproteinases-such as matrix metalloproteinases (MMPs) and a disintegrin and 
      metalloproteinases (ADAMs)-are involved in various diseases of the nervous system 
      but also contribute to nervous system development, synaptic plasticity and 
      neuroregeneration upon injury. MMPs and ADAMs proteolytically cleave many 
      substrates including extracellular matrix components but also signaling molecules 
      and receptors. During neuroinfectious disease with associated neuroinflammation, 
      MMPs and ADAMs regulate blood-brain barrier breakdown, bacterial invasion, 
      neutrophil infiltration and cytokine signaling. Specific and broad-spectrum 
      inhibitors for MMPs and ADAMs have experimentally been shown to decrease 
      neuroinflammation and brain damage in diseases with excessive neuroinflammation 
      as a common denominator, such as pneumococcal meningitis and multiple sclerosis, 
      thereby improving the disease outcome. Timing of metalloproteinase inhibition 
      appears to be critical to effectively target the cascade of pathophysiological 
      processes leading to brain damage without inhibiting the neuroregenerative 
      effects of metalloproteinases. As the critical role of metalloproteinases in 
      neuronal repair mechanisms and regeneration was only lately recognized, the 
      original idea of chronic MMP inhibition needs to be conceptually revised. 
      Recently accumulated research urges for a second chance of metalloproteinase 
      inhibitors, which-when correctly applied and dosed-harbor the potential to 
      improve the outcome of different neuroinflammatory diseases.
FAU - Muri, Lukas
AU  - Muri L
AD  - Neuroinfection Laboratory, Institute for Infectious Diseases, University of Bern, 
      Friedbuhlstrasse 51, 3001, Bern, Switzerland.
AD  - Graduate School for Cellular and Biomedical Sciences (GCB), University of Bern, 
      Freiestrasse 1, 3012, Bern, Switzerland.
FAU - Leppert, David
AU  - Leppert D
AD  - Department of Neurology, University Hospital Basel, Petersgraben 4, 4031, Basel, 
      Switzerland.
FAU - Grandgirard, Denis
AU  - Grandgirard D
AD  - Neuroinfection Laboratory, Institute for Infectious Diseases, University of Bern, 
      Friedbuhlstrasse 51, 3001, Bern, Switzerland.
FAU - Leib, Stephen L
AU  - Leib SL
AUID- ORCID: 0000-0002-1106-6123
AD  - Neuroinfection Laboratory, Institute for Infectious Diseases, University of Bern, 
      Friedbuhlstrasse 51, 3001, Bern, Switzerland. stephen.leib@ifik.unibe.ch.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20190606
PL  - Switzerland
TA  - Cell Mol Life Sci
JT  - Cellular and molecular life sciences : CMLS
JID - 9705402
RN  - 0 (Cytokines)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
MH  - ADAM Proteins/*metabolism
MH  - Blood-Brain Barrier/metabolism
MH  - Cytokines/metabolism
MH  - Humans
MH  - Matrix Metalloproteinases/*metabolism
MH  - Multiple Sclerosis/metabolism/*pathology
MH  - Nervous System Diseases/metabolism/*pathology
MH  - Neurons/metabolism
MH  - Neutrophils/cytology/immunology/metabolism
MH  - Signal Transduction
PMC - PMC7079810
OTO - NOTNLM
OT  - Bacterial meningitis
OT  - MMP
OT  - Metalloproteinase
OT  - Multiple sclerosis
OT  - Neuroinfection
OT  - Neuroinflammation
EDAT- 2019/06/07 06:00
MHDA- 2019/07/30 06:00
PMCR- 2020/03/18
CRDT- 2019/06/08 06:00
PHST- 2019/05/23 00:00 [received]
PHST- 2019/05/29 00:00 [accepted]
PHST- 2019/05/23 00:00 [revised]
PHST- 2019/06/07 06:00 [pubmed]
PHST- 2019/07/30 06:00 [medline]
PHST- 2019/06/08 06:00 [entrez]
PHST- 2020/03/18 00:00 [pmc-release]
AID - 10.1007/s00018-019-03174-6 [pii]
AID - 3174 [pii]
AID - 10.1007/s00018-019-03174-6 [doi]
PST - ppublish
SO  - Cell Mol Life Sci. 2019 Aug;76(16):3097-3116. doi: 10.1007/s00018-019-03174-6. 
      Epub 2019 Jun 6.