title: Endogenous and synthetic MMP inhibitors in CNS physiopathology.
abstract: Matrix metalloproteinases (MMPs, including the membrane-type MMPs (MT-MMPs)), a disintegrin and metalloproteinase (ADAM), and ADAM with thrombospondin motifs belong to the metzincins, a subclass of metalloproteinases that contain a Met residue and a Zn(2+) ion at the catalytic site necessary for enzymatic reaction. MMP proteolytic activity is mainly controlled by their natural tissue inhibitors of metalloproteinase (TIMP). A number of synthetic inhibitors have been developed to control deleterious MMP activity. The roles of MMPs and some of their ECM substrates in CNS physiology and pathology are covered by other chapters of the present volume and will thus not be addressed in depth. This chapter will focus (i) on the endogenous MMP inhibitors in the CNS, (ii) on MMP and TIMP regulations in three large classes of neuropathologic processes (inflammatory, neurodegenerative, and infectious), and (iii) on synthetic inhibitors of MMPs and the perspective of their use in different brain diseases.
authors.affiliation: Aix Marseille Université, CNRS, UMR 7259, NICN, 13344, Marseille, France; Neurology and Neuropsychology Department, AP-HM, Marseille, France.
authors.forename: Kévin
authors.initials: K
authors.lastname: Baranger
authors.affiliation: Aix Marseille Université, CNRS, UMR 7259, NICN, 13344, Marseille, France.
authors.forename: Santiago
authors.initials: S
authors.lastname: Rivera
authors.affiliation: Neuroinfection Laboratory, Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
authors.forename: Fabian D
authors.initials: FD
authors.lastname: Liechti
authors.affiliation: Neuroinfection Laboratory, Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
authors.forename: Denis
authors.initials: D
authors.lastname: Grandgirard
authors.affiliation: Iproteos S.L., Barcelona, Spain.
authors.forename: Judit
authors.initials: J
authors.lastname: Bigas
authors.affiliation: Iproteos S.L., Barcelona, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Seco
authors.affiliation: Iproteos S.L., Barcelona, Spain; Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Tarrago
authors.affiliation: Neuroinfection Laboratory, Institute for Infectious Diseases, University of Bern, Bern, Switzerland; Biology Division, Spiez Laboratory, Swiss Federal Office for Civil Protection, Spiez, Switzerland.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Leib
authors.affiliation: Aix Marseille Université, CNRS, UMR 7259, NICN, 13344, Marseille, France. Electronic address: michel.khrestchatisky@univ-amu.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Khrestchatisky
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000378:metabolism* / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases
keywords: Alzheimer's disease; EAE; Synthetic MMP inhibitors; bacterial meningitis; multiple sclerosis