title: The multifaceted role of metalloproteinases in physiological and pathological conditions in embryonic and adult brains.
abstract: Matrix metalloproteinases (MMPs) are a large family of ubiquitous extracellular endopeptidases, which play important roles in a variety of physiological and pathological conditions, from the embryonic stages throughout adult life. Their extraordinary physiological "success" is due to concomitant broad substrate specificities and strict regulation of their expression, activation and inhibition levels. In recent years, MMPs have gained increasing attention as significant effectors in various aspects of central nervous system (CNS) physiology. Most importantly, they have been recognized as main players in a variety of brain disorders having different etiologies and evolution. A common aspect of these pathologies is the development of acute or chronic neuroinflammation. MMPs play an integral part in determining the result of neuroinflammation, in some cases turning its beneficial outcome into a harmful one. This review summarizes the most relevant studies concerning the physiology of MMPs, highlighting their involvement in both the developing and mature CNS, in long-lasting and acute brain diseases and, finally, in nervous system repair. Recently, a concerted effort has been made in identifying therapeutic strategies for major brain diseases by targeting MMP activities. However, from this revision of the literature appears clear that MMPs have multifaceted functional characteristics, which modulate physiological processes in multiple ways and with multiple consequences. Therefore, when choosing MMPs as possible targets, great care must be taken to evaluate the delicate balance between their activation and inhibition and to determine at which stage of the disease and at what level they become active in order maximize chances of success.
authors.affiliation: Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Dip. di Biologia e Biotecnologie "Charles Darwin", Sapienza Università di Roma, P.le Aldo Moro 5, 00185 Roma, Italy; Center for Research in Neurobiology "Daniel Bovet", Sapienza Università di Roma, P.le Aldo Moro 5, 00185 Roma, Italy. Electronic address: egle.destefano@uniroma1.it.
authors.forename: Maria Egle
authors.initials: ME
authors.lastname: De Stefano
authors.affiliation: Clinical and Experimental Neuroscience Unit, University of Murcia, Campus Mare Nostrum, 30071 Murcia, Spain; Biomedical Research Institute of Murcia (IMIB), University of Murcia, Campus Mare Nostrum, 30071 Murcia, Spain; Institute of Research on Aging, School of Medicine, University of Murcia, Campus Mare Nostrum, 30071 Murcia, Spain. Electronic address: mtherrer@um.es.
authors.forename: Maria Trinidad
authors.initials: MT
authors.lastname: Herrero
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology*; D006801:Humans; D020782:Matrix Metalloproteinases
chemical_list: D020782:Matrix Metalloproteinases
keywords: Brain disorders; Development; Metalloproteinases; Nervous system repair; Neurodegenerative diseases; Neuroinflammation