Platelet Endothelial Cell Adhesion Molecule-1 and Oligodendrogenesis: Significance in Alcohol Use Disorders

Abstract

Alcoholism is a chronic relapsing disorder with few therapeutic strategies that address the core pathophysiology. Brain tissue loss and oxidative damage are key components of alcoholism, such that reversal of these phenomena may help break the addictive cycle in alcohol use disorder (AUD). The current review focuses on platelet endothelial cell adhesion molecule 1 (PECAM-1), a key modulator of the cerebral endothelial integrity and neuroinflammation, and a targetable transmembrane protein whose interaction within AUD has not been well explored. The current review will elaborate on the function of PECAM-1 in physiology and pathology and infer its contribution in AUD neuropathology. Recent research reveals that oligodendrocytes, whose primary function is myelination of neurons in the brain, are a key component in new learning and adaptation to environmental challenges. The current review briefly introduces the role of oligodendrocytes in healthy physiology and neuropathology. Importantly, we will highlight the recent evidence of dysregulation of oligodendrocytes in the context of AUD and then discuss their potential interaction with PECAM-1 on the cerebral endothelium.

Differential Expression of CD31 and Von Willebrand Factor on Endothelial Cells in Different Regions of the Human Brain: Potential Implications for Cerebral Malaria Pathogenesis

“…Thus, we can speculate that there is regional variance in the maintenance of the BBB mediated by CD31. Thus, the modulation of BBB integrity in response to injury such as inflammation or stress [53], especially in the grey matter, still needs to be further characterized.…”

Endothelial dysfunction in neuroprogressive disorders—causes and suggested treatments

“…Levels of phosphorylation also determine the activity of PECAM-1. In this instance, phosphorylation levels of the so-called tyrosine-based inhibition sequence (ITAM) largely determine its signalling capabilities, which regulate actin cytoskeleton rearrangement, tight junction integrity and intracellular signalling pathways, reviewed in [ 126 ]. Briefly, in physiological conditions, phosphorylation of ITAM leads to the recruitment of SHP-2 and subsequent phosphorylation and activation of MAPK/ERK pathways and STAT-3, ultimately leading to the inhibition of NF-κB activity [ 127 – 129 ].…”

Alcohol-Mediated Organ Damages: Heart and Brain

“…Endothelial PECAM-1 is a cell adhesion molecule that allows for the interaction of immune cells and the endothelium which facilitates the transmigration of leukocytes and thus contributes to the endothelial cell permeability barrier (Lertkiatmongkol et al, 2016 ); endothelial PECAM-1 (not Leukocytic PECAM-1) is the key regulatory component in this process (Wong and Dorovini-Zis, 1996 ; Lertkiatmongkol et al, 2016 ; Mandyam et al, 2017 ). It was reported that PECAM-1 may contribute to BBB damage, decline in oligodendrogenesis, demyelination and subsequent cognitive dysfunction (Mandyam et al, 2017 ). More over PECAM-1 could enhance the expression of NF-kB, a proinflammatory transcription factor which is produced under conditions of oxidative stress.…”

“…More over PECAM-1 could enhance the expression of NF-kB, a proinflammatory transcription factor which is produced under conditions of oxidative stress. Upregulation of NF-kB signaling further enhances the immune response, and this, in conjunction with impaired vascular endothelial integrity, could further facilitate the infiltration of leukocytes into the brain (Mandyam et al, 2017 ).…”