Chapter 20. Cell Adhesion Integrins as Pharmaceutical Targets

Publisher Summary Integrin research is rapidly evolving. Anti-platelet agents are in the clinic and discovery efforts are ranging across a spectrum of opportunities for the treatment of disease, both metabolic and infectious. The complex, dynamically regulated phenotypic expression of plasma membrane linked glycoprotein and carbohydrate molecules and their ability to uniquely recognize soluble and insoluble ligands helps define the biological basis of current concepts of development, life, and death. As understanding of the pivotal role of cell adhesion and communication in normal life processes improves, further discernment of the consequences of atypical adhesion and communication becomes possible. The promise of more lucid molecular pathology is modification of disease states through drug treatment. This chapter discusses the integrin class of cell adhesion molecules. The focus remains toward the pathologies for which disease modifying agents could be developed based on the understanding of the specific molecular interactions. The integrin superfamily is made up of structurally and functionally related glycoproteins distributed over three families— namely, the very late antigens (VLA) family (β 1 ), the Leucam family (β 2 ), and the cytoadhesin family (β 3 ). Integrins are α,β heterodimeric, transmembrane receptor molecules found in combinations on every mammalian cell type except red blood cells. There are 15 α subunits and 8 β subunits that are noncovalently linked and expressed on the surfaces of cells in combination. The integrin name has been derived from their role in “integrating” the extracellular matrix (ECM) with the cytoskeleton.