Premium
Blood–brain barrier: A novel therapeutic target in multiple sclerosis
Author(s) -
Kuwahara Hiroya,
Nishina Kazutaka,
Yokota Takanori
Publication year - 2015
Publication title -
clinical and experimental neuroimmunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.297
H-Index - 15
ISSN - 1759-1961
DOI - 10.1111/cen3.12212
Subject(s) - cell adhesion molecule , blood–brain barrier , microbiology and biotechnology , neural cell adhesion molecule , soluble cell adhesion molecules , cell adhesion , selectin , adhesion , endothelial stem cell , cell–cell interaction , multiple sclerosis , intercellular adhesion molecule 1 , immunology , biology , central nervous system , chemistry , neuroscience , in vitro , biochemistry , organic chemistry
Abstract Multiple sclerosis is an autoimmune inflammatory disorder of the central nervous system, and the entrance of pathogenic lymphocytes from blood circulation into the brain across the blood–brain barrier ( BBB ) is accepted as the initial step of pathogenesis. The migration of lymphocytes across the BBB is mediated by their sequential interactions with the brain microvascular endothelial cells, the central component of the BBB , including rolling (loose attachment), adhesion (firm attachment), crawling and transmigration. There are a variety of cell adhesion molecules that are expressed on brain microvascular endothelial cells and are involved in this process. The selectins are assumed to be associated with the rolling of lymphocytes. Vascular cell adhesion molecule‐1 contributes to the adhesion of lymphocytes by binding to very late antigen‐4 on their surface after the stimulation by cytokines. Intercellular adhesion molecule‐1 acts for the adhesion as well and the subsequent crawling of lymphocytes by binding to leukocyte function‐associated antigen‐1 on their surface. Activated leukocyte cell adhesion molecule, melanoma cell adhesion molecule, platelet endothelial cell adhesion molecule‐1, nerve injury‐induced protein‐1 and vascular adhesion protein‐1 are also considered to influence the migratory process of lymphocytes across the BBB , although the detailed mechanisms are not elucidated. Here we review the pathophysiology of multiple sclerosis at the BBB to present a possible molecular targeted therapy in the future, especially focused on the molecules expressing at the brain microvascular endothelial cells.