Structure-function relationships of PEDF

• Published in: Current molecular medicine Vol. 10; no. 3; p. 302
• Main Authors: Kawaguchi, T, Yamagishi, S-I, Sata, M
• Format: Journal Article
• Language: English
• Published: Netherlands 01.04.2010
• Subjects: Angiogenesis Inhibitors - chemistry; Angiogenesis Inhibitors - metabolism; Angiogenesis Inhibitors - pharmacology; Binding Sites; Capillary Permeability - drug effects; Cell Nucleus - metabolism; Extracellular Matrix - metabolism; Eye Proteins - chemistry; Eye Proteins - genetics; Eye Proteins - metabolism; Eye Proteins - pharmacology; Glucose - metabolism; Lipid Metabolism - drug effects; Nerve Growth Factors - chemistry; Nerve Growth Factors - genetics; Nerve Growth Factors - metabolism; Nerve Growth Factors - pharmacology; Protease Inhibitors - chemistry; Protease Inhibitors - metabolism; Protease Inhibitors - pharmacology; Receptors, Neuropeptide - genetics; Receptors, Neuropeptide - metabolism; Serpins - chemistry; Serpins - genetics; Serpins - metabolism; Serpins - pharmacology
• ISSN: 1875-5666
• DOI: 10.2174/156652410791065255

Pigment epithelial-derived factor (PEDF) is a 50-kDa secreted glycoprotein that belongs to the noninhibitory serpin. It has an alpha/beta core serine-protease inhibitor domain, 3 major beta-sheets, and 10 alpha-helices. Although PEDF does not inhibit either serine or cysteine proteinases, PEDF exerts diverse physiological activities including anti-angiogenesis, anti-vasopermeability, anti-tumor, and neurotrophic activities. Recent studies have shown that a variety of peptides derived from PEDF possess activities similar to those of the parent molecule through interactions with the extracellular matrix, binding to PEDF receptors, nuclear localization and phosphorylation. Thus, peptides derived from PEDF have therapeutic potential for various diseases and therefore, it is important to clarify the structure-function relationship of PEDF. In this review, we summarize structural features of PEDF that could affect various target organs such as blood vessels, tumors, and the central nervous system. In addition, since PEDF is recently identified as a regulator for glucose and lipid metabolism, we also discuss PEDF structures specially related to insulin-sensitizing and triglyceridereducing properties.