Metalloproteinase inhibitors: biological actions and therapeutic opportunities

Tissue inhibitors of metalloproteinases (TIMPs) are the major cellular inhibitors of the matrix metalloproteinase (MMP) sub-family, exhibiting varying efficacy against different members, as well as different tissue expression patterns and modes of regulation. Other proteins have modest inhibitory activity against some of the MMPs, including domains of netrins, the procollagen C-terminal proteinase enhancer (PCPE), the reversion-inducing cysteine-rich protein with Kazal motifs (RECK), and tissue factor pathway inhibitor (TFPI-2), but their physiological significance is not at all clear. Alpha2-macroglobulin, thrombospondin-1 and thrombospondin-2 can bind to some MMPs and act as agents for their removal from the…