TY - JOUR

T1 - Role of syndecans in lipid metabolism and human diseases

AU - Leonova, Elena I.

AU - Galzitskaya, Oxana V.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Syndecans are transmembrane heparan sulfate proteoglycans involved in the regulation of cell growth, differentiation, adhesion, neuronal development, and lipid metabolism. Syndecans are expressed in a tissue-specifi c manner to facilitate diverse cellular processes. As receptors and coreceptors, syndecans provide promising therapeutic targets that bind to a variety of physiologically important ligands. Negatively charged glycosaminoglycan chains of syndecans, located in the extracellular compartment, are critical for such binding. Functions of syndecans are as diverse as their ligands. For example, hepatic syndecan-1 mediates clearance of triglyceride-rich lipoproteins. Syndecan-2 promotes localization of Alzheimer’s amyloid Aβ peptide to the cell surface, which is proposed to contribute to amyloid plaque formation. Syndecan-3 helps co-localize the appetite-regulating melanocortin-4 receptor with its agonist, leading to an increased appetite. Finally, syndecan-4 initiates the capture of modifi ed low-density lipoproteins by macrophages and thereby promotes the atheroma formation. We hypothesize that syndecan modifi cations such as desulfation of glycosaminoglycan chains may contribute to a wide range of diseases, from atherosclerosis to type 2 diabetes. At the same time, desulfated syndecans may have benefi cial effects, as they can inhibit amyloid plaque formation or decrease the appetite. Despite considerable progress in understanding diverse functions of syndecans, the complex physiological roles of this intriguing family of proteoglycans are far from clear. Additional studies of syndecans may potentially help develop novel therapeutic approaches and diagnostic tools to alleviate complex human diseases such as cardiovascular and Alzheimer’s diseases.

AB - Syndecans are transmembrane heparan sulfate proteoglycans involved in the regulation of cell growth, differentiation, adhesion, neuronal development, and lipid metabolism. Syndecans are expressed in a tissue-specifi c manner to facilitate diverse cellular processes. As receptors and coreceptors, syndecans provide promising therapeutic targets that bind to a variety of physiologically important ligands. Negatively charged glycosaminoglycan chains of syndecans, located in the extracellular compartment, are critical for such binding. Functions of syndecans are as diverse as their ligands. For example, hepatic syndecan-1 mediates clearance of triglyceride-rich lipoproteins. Syndecan-2 promotes localization of Alzheimer’s amyloid Aβ peptide to the cell surface, which is proposed to contribute to amyloid plaque formation. Syndecan-3 helps co-localize the appetite-regulating melanocortin-4 receptor with its agonist, leading to an increased appetite. Finally, syndecan-4 initiates the capture of modifi ed low-density lipoproteins by macrophages and thereby promotes the atheroma formation. We hypothesize that syndecan modifi cations such as desulfation of glycosaminoglycan chains may contribute to a wide range of diseases, from atherosclerosis to type 2 diabetes. At the same time, desulfated syndecans may have benefi cial effects, as they can inhibit amyloid plaque formation or decrease the appetite. Despite considerable progress in understanding diverse functions of syndecans, the complex physiological roles of this intriguing family of proteoglycans are far from clear. Additional studies of syndecans may potentially help develop novel therapeutic approaches and diagnostic tools to alleviate complex human diseases such as cardiovascular and Alzheimer’s diseases.

KW - Alzheimer’s disease

KW - Apolipoproteins

KW - Atherosclerosis

KW - Heparan sulfate proteoglycans

KW - Obesity

KW - Shedding of syndecans

UR - http://www.scopus.com/inward/record.url?scp=84936767747&partnerID=8YFLogxK

U2 - 10.1007/978-3-319-17344-3_10

DO - 10.1007/978-3-319-17344-3_10

M3 - Article

C2 - 26149933

AN - SCOPUS:84936767747

VL - 855

SP - 241

EP - 258

JO - Advances in Experimental Medicine and Biology

JF - Advances in Experimental Medicine and Biology

SN - 0065-2598

ER -