Endogenous and synthetic MMP inhibitors in CNS physiopathology

authors

• Baranger Kévin
• Rivera Santiago
• Liechti Fabian D.
• Grandgirard Denis
• Bigas Judit
• Seco Jesús
• Tarrago Teresa
• Leib Stephen L.
• Khrestchatisky Michel

keywords

• Animals
• Matrix Metalloproteinase Inhibitors
• Matrix Metalloproteinases
• Alzheimer's disease
• Bacterial meningitis
• Central Nervous System
• EAE
• Multiple sclerosis
• Synthetic MMP inhibitors
• Tissue Inhibitor of Metalloproteinases

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.

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