title: Heparanase: a rainbow pharmacological target associated to multiple pathologies including rare diseases.
abstract: In recent years, heparanase has attracted considerable attention as a promising target for innovative pharmacological applications. Heparanase is a multifaceted protein endowed with enzymatic activity, as an endo-β-D-glucuronidase, and nonenzymatic functions. It is responsible for the cleavage of heparan sulfate side chains of proteoglycans, resulting in structural alterations of the extracellular matrix. Heparanase appears to be involved in major human diseases, from the most studied tumors to chronic inflammation, diabetic nephropathy, bone osteolysis, thrombosis and atherosclerosis, in addition to more recent investigation in various rare diseases. The present review provides an overview on heparanase, its biological role, inhibitors and possible clinical applications, covering the latest findings in these areas.
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Parma, Parco Area delle Scienze 27/A. I-43124 Parma, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Rivara
authors.affiliation: Biotechnology, R&D Sigma-Tau IFR S.p.A., via Pontina, km 30,400. I-00071 Pomezia (RM), Italy.
authors.forename: Ferdinando M
authors.initials: FM
authors.lastname: Milazzo
authors.affiliation: Medicinal Chemistry, R&D Sigma-Tau IFR S.p.A., via Pontina, km 30,400. I-00071 Pomezia (RM), Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giannini
mesh_terms: D050197:Atherosclerosis / Q000188:drug therapy / Q000201:enzymology; D001862:Bone Resorption / Q000188:drug therapy / Q000201:enzymology; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000201:enzymology; D005966:Glucuronidase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000201:enzymology; D035583:Rare Diseases / Q000188:drug therapy / Q000201:enzymology; D013379:Substrate Specificity; D013927:Thrombosis / Q000188:drug therapy / Q000201:enzymology; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D000099175:Heparanase
keywords: angiogenesis; cancer and metastasis; endo-β-D-glucuronidase; heparanase; heparanase in vitro assays; heparanase inhibitors; heparanase structure; inflammation; modified heparins; rare diseases