Matrix metalloproteinase-3 in the central nervous system: a look on the bright side

Abstract

Matrix metalloproteinases (MMPs) are a large family of proteases involved in many cell-matrix and cell-cell signalling processes through activation, inactivation or release of extracellular matrix (ECM) and non-ECM molecules, such as growth factors and receptors. Uncontrolled MMP activities underlie the pathophysiology of many disorders. Also matrix metalloproteinase-3 (MMP-3) or stromelysin-1 contributes to several pathologies, such as cancer, asthma and rheumatoid arthritis, and has also been associated with neurodegenerative diseases like Alzheimer's disease, Parkinson's disease and multiple sclerosis. However, based on defined MMP spatiotemporal expression patterns, the identification of novel candidate molecular targets and in vitro and in vivo studies, a beneficial role for MMPs in CNS physiology and recovery is emerging. The main purpose of this review is to shed light on the recently identified roles of MMP-3 in normal brain development and in plasticity and regeneration after CNS injury and disease. As such, MMP-3 is correlated with neuronal migration and neurite outgrowth and guidance in the developing CNS and contributes to synaptic plasticity and learning in the adult CNS. Moreover, a strict spatiotemporal MMP-3 up-regulation in the injured or diseased CNS might support remyelination and neuroprotection, as well as genesis and migration of stem cells in the damaged brain.