Multiphasic roles for matrix metalloproteinases after stroke.
Matrix metalloproteinases (MMPs) comprise a family of zinc endopeptidases that play major roles in the physiology and pathology of the mammalian central nervous system (CNS). These proteinases are evolutionarily conserved as modulators of extracellular matrix during CNS development. After acute tissue injury such as that which occurs after stroke, MMPs become dysregulated and subsequently mediate acute neurovascular disruption and parenchymal destruction. Data from gene knockout models and pharmacologic experiments suggest that MMPs may be attractive therapeutic targets for stroke. However, emerging data now also suggest that some aspects of MMP activity during the delayed neuroinflammatory response may contribute to remodelling and stroke recovery. Ultimately, a more nuanced approach to modifying the MMP response after stroke may be needed in order to optimize inhibition during acute stages of injury without interfering with beneficial endogenous mechanisms of neurovascular remodelling.
Rosell
Anna
A
Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. anna.rosell@gmail.com
Lo
Eng H
EH
D000818:Animals; D015415:Biomarkers; D002545:Brain Ischemia / Q000201:enzymology / Q000209:etiology; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000502:physiology*; D009473:Neuronal Plasticity; D011480:Protease Inhibitors / Q000627:therapeutic use; D020521:Stroke / Q000188:drug therapy / Q000201:enzymology / Q000209:etiology*
D015415:Biomarkers; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D020782:Matrix Metalloproteinases