Adhesion Molecules in CNS Disorders: Biomarker and Therapeutic Targets

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 pro-inflammatory 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 with in 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 (VAP-1), a novel adhesion molecule and endothelial cell surface enzyme, has been implicated as a brake during leukocyte extravasation. In this review, we summarize the functions of traditional adhesion molecules as well as VAP-1 in the leukocyte adhesion cascade. We also discuss the diagnostic and therapeutic potential of adhesion molecules in CNS disorders.

Sildenafil ameliorates Alzheimer disease via the modulation of vascular endothelial growth factor and vascular cell adhesion molecule-1 in rats

“…3,4 Several interacting endothelial cell mediators including nitric oxide (NO), vascular endothelial growth factor (VEGF), and vascular cell adhesion molecule-1 (VCAM-1) were implicated in several neuronal effects including cell proliferation, angiogenesis, inflammation, and neurological impact on glial and neuronal cells. 5,6 AD was associated with increased vascular inflammation, as evidenced by elevated expression and localization of inflammatory markers such as VCAM-1 and Tumor necrosis factor-a (TNF-a) surrounding AD-plaques. 7 Previous studies reported that decline in VEGF-A was correlated with the aggravation of AD pathology indicated by the high level of a-synuclein.…”

Crocus Sativusand Its Active Compound, Crocin Inhibits the Endothelial Activation and Monocyte-Endothelial Cells Interaction in Stimulated Human Coronary Artery Endothelial Cells

“…sICAM-1 is an endothelial and leukocyte associated transmembrane protein renowned for its role in maintaining cell-cell interactions and promoting leukocyte endothelial transmigration. Activated endothelium releases soluble adhesion molecules and is therefore used to measure endothelial activation by measuring fluid-phase of those molecules(20). Previous study reported that another saffron compound, crocetin, can reduce leukocyte adhesion to endothelial cells by decreasing the expression of ICAM-1(18).…”

Deficiency of TREK-1 potassium channel exacerbates blood-brain barrier damage and neuroinflammation after intracerebral hemorrhage in mice

“…They are low expressed mainly by endothelial cells under normal condition. In the inflammatory process, the expression of these adhesion molecules can be upregulated to promote leukocyte adhesion and blood-derived monocytes transmigration [43]. The upregulation of these molecules has been identified to participate in numerous neurological disorders [44–46].…”