Targeting MMPs in acute and chronic neurological conditions

The matrix metalloproteinases (MMPs) are important enzymes that regulate developmental processes, maintain normal physiology in adulthood and have reparative roles at specific stages after an insult to the nervous system. Conversely, the concordant presence and significant upregulation of several MMP members in virtually all neurological conditions result in pathology. Thus, the MMPs have diverse functions, capable of mediating repair and recovery on the one hand and being involved in producing injury on the other. Therefore, targeting MMPs in neurological conditions has become a complicated challenge. This article highlights the beneficial roles of MMPs in normal and reparative processes within the nervous system and discusses the detriments of MMPs encountered in pathology. We review the availability of MMP inhibitors for clinical use and propose that an important consideration for these inhibitors is timing and duration of their use. With acute injuries where a massive upregulation of several MMPs are observed in the early periods after the insult, early and short-term use of broad spectrum MMP inhibitors would seem logical. In chronic conditions where recurrent insults to the CNS are accompanied by prolonged upregulation of MMPs, thereby necessitating the chronic use of medications, the beneficial effects of MMPs in repair may be compromised by the long-term application of MMP inhibitors. In this review we have used spinal cord injury and multiple sclerosis as examples of acute and chronic neurological conditions, respectively, and we consider the use of MMP inhibitors in these states. Key Words: CNS injury, MMP inhibitors, metalloproteinases, multiple sclerosis, spinal cord injury.