CLDN5

CLDN5 or Claudin-5 is a protein that in humans is encoded by the CLDN5 gene. Claudin-5 is a member of the claudin family, which constitutes integral membrane proteins that are components of the tight junction strands. Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space.

Function

Claudin-5 is specifically expressed in endothelial cells and plays a critical role in controlling the blood-brain barrier (BBB) permeability. It is involved in maintaining the low permeability of the BBB, thus regulating the molecular exchange between the blood and the brain. This function is crucial for the maintenance of the brain's microenvironment and for the protection of the neural tissue from toxins and pathogens.

Structure

The CLDN5 gene encodes a protein that is approximately 22 kDa in size and is composed of four transmembrane domains, two extracellular loops, and N- and C-terminal cytoplasmic tails. The extracellular loops are involved in the formation of tight junctions through homophilic and heterophilic interactions with other claudin proteins.

Clinical Significance

Alterations in the expression or function of claudin-5 have been associated with several pathological conditions. Increased permeability of the BBB, due to reduced expression or dysfunction of claudin-5, has been observed in various neurological disorders, including multiple sclerosis, Alzheimer's disease, and stroke. This disruption can lead to increased infiltration of immune cells and potentially harmful substances into the brain, exacerbating disease progression.

In addition to neurological disorders, changes in claudin-5 expression have been implicated in the metastasis of certain cancers. The downregulation of claudin-5 in endothelial cells of the blood vessels can increase vascular permeability, facilitating the transendothelial migration of cancer cells and contributing to tumor metastasis.

Research and Therapeutic Potential

Given its pivotal role in regulating BBB permeability, claudin-5 has emerged as a potential therapeutic target for diseases associated with BBB dysfunction. Strategies to modulate claudin-5 expression or function could potentially restore BBB integrity and offer therapeutic benefits for neurological disorders and certain cancers.

See Also

• Tight junction
• Blood-brain barrier
• Endothelial cells
• Claudin