A biochemical pathway involved in development also maintains a physiological brain-defence system that is implicated in the autoimmune disease multiple sclerosis (MS).
The blood–brain barrier (BBB) protects the brain by preventing cells and many molecules from entering it, and is disrupted in MS. Signalling between brain cells called astrocytes through the Hedgehog pathway promotes the maturation of cells lining the brain's blood vessels and formation of the BBB.
Alexandre Prat at the University of Montreal in Canada and his group found that inhibiting this pathway in an animal model of MS boosted immune-cell invasion of the brain and increased demyelination — loss of neurons' protective sheath, the hallmark of MS. Stimulating Hedgehog signalling in cultured human cells caused fewer inflammatory T cells to interact with and migrate across blood-vessel cells.
Many patients with MS experience cyclical inflammatory attacks of the brain, and they also have higher levels of Hedgehog signalling. The authors think that this pathway may be involved in rebalancing the immune response after each attack.
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A boost to the brain's barrier. Nature 480, 154 (2011). https://doi.org/10.1038/480154c
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DOI: https://doi.org/10.1038/480154c
