title: Substrate-protecting antiproteolytic agents for the prevention of pathological degradation of connective tissues. A review.
abstract: Connective tissues play an important role in the physiological functions of the organism. The integrity of the macromolecular components of these tissues, also called extracellular matrix, is necessary for their functional efficiency. A number of proteinases present in the organism, and the activity of which increases with age and with several pathologies, specifically degrade the components of the extracellular matrix. For a long time, tentatives for the protection of the matrix-components against degradation were made with low molecular weight inhibitors, not very efficient in vivo and not devoid of inconveniencies. We initiated a different approach for the preservation of the macromolecules of the extracellular matrix against proteolytic degradation with substances which exert an intense antiproteolytic activity not only in vitro, but also in vivo. The particularity of these substances is the fact that they do not act on the enzymes, but combine with the macromolecules. This is the type of combination of substances with the macromolecules of the matrix that prevents their degradation by the proteinases. Because of this affinity of such antiproteolytic agents not for the enzymes but for the substrates, we called them "substrate protectors" (Robert et al., 1979). The aim of the present review is to summarise the essential of our experiments which led to the description of substrate protectors.
authors.affiliation: Laboratoire de recherche ophtalmologique, hôpital Hôtel-Dieu, université Paris-5, 1, place du Parvis-Notre-Dame, 75181 Paris cedex 04, France. robertam2@wanadoo.fr
authors.forename: A-M
authors.initials: AM
authors.lastname: Robert
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D003238:Connective Tissue / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D003240:Connective Tissue Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019610:Cytoprotection / Q000187:drug effects*; D006801:Humans; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D059748:Proteolysis / Q000187:drug effects; D013379:Substrate Specificity
chemical_list: D011480:Protease Inhibitors