Matrix metalloproteinases and their endogenous inhibitors in neuronal physiology of the adult brain

Abstract

More than 20 matrix metalloproteinases (MMPs) and four of their endogenous tissue inhibitors (TIMPs) act together to control tightly temporally restricted, focal proteolysis of extracellular matrix. In the neurons of the adult brain several components of the TIMP/MMP system are expressed and are responsive to changes in neuronal activity. Furthermore, functional studies, especially involving blocking of MMP activities, along with the identification of MMP substrates in the brain strongly suggest that this enzymatic system plays an important physiological role in adult brain neurons, possibly being pivotal for neuronal plasticity.

DDR1 may play a key role in destruction of the blood–brain barrier after cerebral ischemia–reperfusion

“…Studies also showed that invading inflammatory cells can provide the major source of the MMP activity (Kaczmarek et al, 2002). Moreover, MMP-9 is expressed in adult brain neurons and is responsive to changes in neuronal activity (Dzwonek et al, 2004). Combined with the results of previous research (Castro-Sanchez et al, 2011), we hypothesized that MMP-9 overexpression and activation after cerebral ischemic injury may be regulated by its upstream molecule (DDR1) via inflammatory responses, which provided a reliable basis for our next experiments.…”

Epileptiform activity interferes with proteolytic processing of Reelin required for dentate granule cell positioning

“…In fact, after KA treatment, we found a decrease of gelatinolytic (ϭMMP) activity in the ML and GCL by in situ zymography, indicating that KA indeed causes a reduction of MMP activity in the regions where surviving Cajal-Retzius cells are located. It is possible that tissue inhibitors of metalloproteases (TIMPs), known to control the activity of MMPs (42), are involved in the down-regulation of MMP activity in our system. In fact, TIMP-1 expression has been shown to increase rapidly in the hippocampus following seizures (43)(44).…”

The effect of IL-1α on the expression of matrix metalloproteinases, plasminogen activators, and their inhibitors in osteoblastic ROS 17/2.8 cells

“…Four mammalian TIMPs have been cloned and characterized by primary structure and functional analyses (Dzwonek et al, 2004;Lambert et al, 2004). TIMP-1 is secreted as a 28-kDa glycoprotein that binds tightly to the active form of multiple MMPs.…”