Title:An Overview of the α4β1 Integrin and the Potential Therapeutic Role of its Antagonists
Volume: 28
Issue: 29
Author(s): Elenilze F.B. Ferreira , Luciane B. Silva , Josiane V. Cruz, Pedro H.F. Araújo, Njogu M. Kimani, Franco H.A. Leite , Joaquín M. Campos *Cleydson B.R. Santos
Affiliation:
- Department of Pharmaceutical and Organic Chemistry, Faculty of Pharmacy, Campus of Cartuja, University of Granada, 18071 Granada,Spain
Keywords:
Integrin, target, adhesion molecule, CD49d, VLA-4, α4, α4β1 integrin antagonists, extracellular matrix.
Abstract: 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.
