Podocalyxin, a protein found in cells lining the interior of blood vessels, is key for maintaining the integrity of the blood-brain barrier (BBB) in mice with systemic infection, suggesting its potential as a therapeutic target for neurodegenerative diseases such as multiple sclerosis (MS), a study shows.
Disruption of the BBB is a hallmark of various disorders, including MS. This barrier is a natural, highly selective membrane that shields the central nervous system with its cerebrospinal fluid from the general blood circulation. When damaged, the BBB can no longer prevent immune cells and large molecules from entering the central nervous system, which may trigger inflammation and damage to neurons.
The study, “Podocalyxin is required for maintaining blood–brain barrier function during acute inflammation,” was published in the journal PNAS.
Podocalyxin is a protein found universally in most blood vessels in adult vertebrates; however, its function has not been thoroughly assessed.
Researchers at the University of British Columbia (UBC) studied the effects of the loss of podocalyxin in human endothelial cells — which line the interior of blood vessels — grown in the lab, and in mouse models of inflammation.
They detected podocalyxin at high levels in the BBB.
The team deleted the gene providing instructions for podocalyxin in the brain, and measured the BBB’s function in steady-state (normal) conditions and after treatment with lipopolysaccharide (LPS) — a bacterial protein that induces systemic (whole-body) inflammation.
They found that the protein was required to strengthen blood vessels by promoting the formation of cell-cell interactions essential to establishing the cell’s barrier function.
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