Title:Adhesion Molecules in CNS Disorders: Biomarker and Therapeutic Targets
Volume: 12
Issue: 3
Author(s): Qingyi Ma, Sheng Chen, Damon Klebe, John H. Zhang and Jiping Tang
Affiliation:
Keywords:
Adhesion molecule, CNS disorders, leukocyte adhesion cascade, vascular adhesion protein-1.
Abstract: Mounting evidence has been provided regarding the crucial role of leukocyte extravasation and subsequent
inflammatory response in several central nervous system (CNS) disorders. The infiltrated leukocytes release proinflammatory
mediators and activate resident cells, leading to tissue injury. Leukocyte-endothelia interaction is critical for
leukocyte extravasation and migration from the intravascular space into the tissue during inflammation. The basic
physiology of leukocyte-endothelia interaction has been investigated extensively. Traditionally, three kinds of adhesion
molecules, selectin, integrin, and immunoglobulin families, are responsible for this multiple-step interaction. Furthermore,
blocking adhesion molecule function by genetic knockout, antagonizing antibodies, or inhibitory pharmacological drugs
provides neuroprotection, which is associated with a reduction in leukocyte accumulation within the tissue. Detection of
the soluble form of adhesion molecules has also been proven to predict outcomes in CNS disorders. Lately, vascular
adhesion protein-1, a novel adhesion molecule and endothelial cell surface enzyme, has been implicated as a brake in the
rolling step of the adhesion cascade, and also a regulator of leukocyte transmigration step. In this review, we summarize
the functions of traditional adhesion molecules as well as vascular adhesion protein-1in the leukocyte adhesion cascade.
We also discuss the diagnostic and therapeutic potential of adhesion molecules in CNS disorders.