Elenilze F.B. Ferreira , Luciane B. Silva , Josiane V. Cruz, Pedro H.F. Araújo, Njogu M. Kimani, Franco H.A. Leite , Joaquín M. Campos * and Cleydson B.R. Santos Pages 5884 - 5895 ( 12 )
This article presents a simplified view of integrins with emphasis on the α4 (α4β1/VLA-4) integrin. Integrins are heterodimeric proteins expressed on the cell surface of leukocytes that participate in a wide variety of functions, such as survival, growth, differentiation, migration, inflammatory responses, tumour invasion, among others. When the extracellular matrix is degraded or deformed, cells are forced to undergo responsive changes that influence remodelling during physiological and pathological events. Integrins recognize these changes and trigger a series of cellular responses, forming a physical connection between the interior and the outside of the cell. The communication of integrins through the plasma membrane occurs in both directions, from the extracellular to the intracellular (outside-in) and from the intracellular to the extracellular (inside-out). Integrins are valid targets for antibodies and small-molecule antagonists. One example is the monoclonal antibody natalizumab, marketed under the name of TYSABRI®, used in the treatment of recurrent multiple sclerosis, which inhibits the adhesion of α4 integrin to its counter-receptor. α4β1 Integrin antagonists are summarized here, and their utility as therapeutics are also discussed.
Integrin, target, adhesion molecule, CD49d, VLA-4, α4, α4β1 integrin antagonists, extracellular matrix.
Laboratory of Organic Chemistry and Biochemistry, University of the State of Amapa, Macapa 68900-070, AP, Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapa, Macapa 68902-280, AP, Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapa, Macapa 68902-280, AP, Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapa, Macapa 68902-280, AP, Department of Physical Sciences, University of Embu, P.O. Box 6-60100 Embu, Laboratory Cheminformatics and biological assays, State University of Feira de Santana, Feira de Santana, 44036-900 Bahia, Department of Pharmaceutical and Organic Chemistry, Faculty of Pharmacy, Campus of Cartuja, University of Granada, 18071 Granada, Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapa, Macapa 68902-280, AP