title: The many facets of PEDF in drug discovery and disease: a diamond in the rough or split personality disorder?
abstract: BACKGROUND
  Pigment epithelium-derived factor (PEDF) was discovered as a neurotrophic factor secreted by retinal pigment epithelial cells. A decade later, it re-emerged as a powerful angiogenesis inhibitor guarding ocular function. Since then, significant advances were made identifying PEDF's mechanisms, targets and biomedical applications.
  
  
  METHODS
  The authors review several methodologies that have generated significant new information about the potential of PEDF as a drug. Furthermore, the authors review and discuss mechanistic and structure-function analyses combined with the functional mapping of active fragments, which have yielded several short bioactive PEDF peptides. Additionally, the authors present functional studies in knockout animals and human correlates that have provided important information about conditions amenable to PEDF-based therapies.
  
  
  CONCLUSIONS
  Through its four known receptors, PEDF causes a wide range of cellular events vitally important for the organism, which include survival and differentiation, migration and invasion, lipid metabolism and stem cell maintenance. These processes are deregulated in multiple pathological conditions, including cancer, metabolic and cardiovascular disease. PEDF has been successfully used in countless preclinical models of these conditions and human correlates suggest a wide utility of PEDF-based drugs. The most significant clinical application of PEDF, to date, is its potential therapeutic use for age-related macular degeneration. Moreover, PEDF-based gene therapy has advanced to early stage clinical trials. PEDF active fragments have been mapped and used to design short peptide mimetics conferring distinct functions of PEDF, which may address specific clinical problems and become prototype drugs.
authors: St. Louis University School of Medicine, Department of Pathology, St. Louis, Missouri, USA.
authors: Susan E
authors: SE
authors: Craword
authors: Philip
authors: P
authors: Fitchev
authors: Dorina
authors: D
authors: Veliceasa
authors: Olga V
authors: OV
authors: Volpert
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D005136:Eye Proteins / Q000627:therapeutic use*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008268:Macular Degeneration / Q000188:drug therapy*; D008659:Metabolic Diseases / Q000188:drug therapy; D023421:Models, Animal; D009369:Neoplasms / Q000188:drug therapy; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D011480:Protease Inhibitors / Q000627:therapeutic use*; D015843:Serpins / Q000627:therapeutic use*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D020533:Angiogenesis Inhibitors; D005136:Eye Proteins; D009414:Nerve Growth Factors; D011480:Protease Inhibitors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor