The Role of Cytoskeleton Integrins in Multiple Sclerosis: A Key to Understanding Blood-Brain Barrier Disruption

Multiple sclerosis (MS) is a chronic and debilitating autoimmune disease that affects the central nervous system (CNS). The disease is characterized by the destruction of the protective myelin sheath surrounding nerve fibers, leading to communication disruptions between the brain and the rest of the body. The blood-brain barrier (BBB), a critical component of the CNS, plays a crucial role in maintaining the integrity of the CNS by regulating the passage of substances between the blood and the brain. Recent studies have highlighted the importance of cytoskeleton integrins in the context of MS, particularly in relation to BBB disruption.

Cytoskeleton integrins are a class of proteins that are embedded in the cytoplasmic side of the plasma membrane of cells. These proteins are responsible for linking the cytoskeleton to the extracellular matrix (ECM), which is a complex network of proteins and carbohydrates that provides structural support and signaling cues to cells. In the context of MS, cytoskeleton integrins have been shown to play a critical role in the regulation of BBB permeability.

The BBB is composed of specialized endothelial cells that are anchored to the basement membrane by cell adhesion molecules (CAMs). These CAMs, including integrins, are responsible for maintaining the integrity of the BBB by regulating the passage of substances between the blood and the brain. In MS, the disruption of the BBB is thought to be a key factor in the development of the disease. Recent studies have shown that cytoskeleton integrins, particularly β1 integrin, are involved in the regulation of BBB permeability in MS.

One study published in the journal International Journal of Molecular Sciences found that β1 integrin is upregulated in the endothelial cells of MS patients and is associated with increased BBB permeability. The study also found that β1 integrin is involved in the regulation of the expression of adhesion molecules, such as ICAM-1 and VCAM-1, which are critical for the recruitment of immune cells to the CNS. The upregulation of β1 integrin in MS patients may contribute to the disruption of the BBB, allowing immune cells to penetrate the CNS and exacerbate the disease.

Another study published in Fluids and Barriers of the CNS found that the deletion of β1 integrin in endothelial cells leads to a significant decrease in BBB integrity. The study also found that the deletion of β1 integrin results in the downregulation of the expression of laminin, a critical ECM protein that is involved in the regulation of BBB permeability. These findings suggest that β1 integrin plays a critical role in the maintenance of BBB integrity and that its disruption may contribute to the development of MS.

In conclusion, recent studies have highlighted the importance of cytoskeleton integrins, particularly β1 integrin, in the context of MS. The disruption of β1 integrin has been shown to contribute to the disruption of the BBB, allowing immune cells to penetrate the CNS and exacerbate the disease. Further research is needed to fully understand the role of cytoskeleton integrins in MS and to identify potential therapeutic targets for the treatment of the disease.

Reference:
Pyka-Fościak, G., Lis, G. J., & Litwin, J. A. (2022). Adhesion molecule profile and the effect of anti-VLA-4 mAb treatment in experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. International Journal of Molecular Sciences, 23(9), 4637.
Halder, S. K., Delorme-Walker, V. D., & Milner, R. (2023). β1 integrin is essential for blood–brain barrier integrity under stable and vascular remodelling conditions; effects differ with age. Fluids and Barriers of the CNS, 20(1), 52.