Matrix metalloproteinase (MMP) system in brain: identification and characterization of brain-specific MMP highly expressed in cerebellum

The matrix metalloproteinase (MMP) family, comprising more than 20 isoforms , modulates the extracellular milieu by degrading extracellular matrix (ECM ) proteins. Because MMP is one of the few groups of proteinases capable of hydrolysing insoluble fibrillar proteins, they are likely to play crucial r oles in regulating both normal and pathophysiological processes in the brai n. However, little is yet known about their possible neuronal functions due presumably to their unusual redundancy and to the absence of a complete ca talogue of isoforms. As an initial step in understanding the MMP system in the brain, we analysed an expression spectrum of MMP in rat brain using RT- PCR and discovered a novel brain-specific MMP, MT5-MMP. MT5-MMP was the pre dominant species among the nongelatinase-type isoforms in brain. MT5-MMP, p resent in all brain tissues examined, was most strongly expressed in cerebe llum and was localized in the membranous structures of expressing neurons, as assessed biochemically and immunohistochemically. In cerebellum, its exp ression was regulated developmentally and was closely associated with dendr itic tree formation of Purkinje cells, suggesting that MT5-MMP may contribu te to neuronal development. Furthermore, its stable postdevelopmental expre ssion and colocalization with senile plaques in Alzheimer brain indicates p ossible roles in neuronal remodeling naturally occurring in adulthood and i n regulating pathophysiological processes associated with advanced age.