The TIMPs tango with MMPs and more in the central nervous system

J Neurosci Res. 2004 Jan 1;75(1):1-11. doi: 10.1002/jnr.10836.


The matrix metalloproteinases (MMPs) are a family of zinc-dependent extracellular proteases that have been implicated in CNS development and disease. Crucial homeostatic regulation of MMPs is mediated through the expression and actions of the tissue inhibitors of metalloproteinases (TIMPs). Although the TIMPs are recognized inhibitors of the MMPs, recent studies have revealed that these proteins also can exhibit biological activities that are distinct from their interactions with or inhibition of the MMPs. With our understanding of the roles of the TIMPs in the CNS continuously emerging, this review examines the current state of knowledge regarding the multifarious and novel functions of this family of proteins, with particular attention to their increasing potential in the development, plasticity, and pathology of the CNS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Brain Ischemia / metabolism
  • Central Nervous System / enzymology
  • Central Nervous System / growth & development
  • Central Nervous System / metabolism*
  • Encephalitis / metabolism
  • Gene Expression Regulation, Developmental
  • Humans
  • Matrix Metalloproteinases / metabolism*
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism
  • Tissue Inhibitor of Metalloproteinases / classification
  • Tissue Inhibitor of Metalloproteinases / genetics
  • Tissue Inhibitor of Metalloproteinases / metabolism*


  • Tissue Inhibitor of Metalloproteinases
  • Matrix Metalloproteinases