Sci. Signal., 3 January 2012
Neuroscience Hedgehogs Man the Gate
Kristen L. Mueller
Science, AAAS, Washington, DC 20005, USA
The blood-brain barrier (BBB) is composed of tightly bound endothelial cells and perivascular astrocytes and keeps potentially harmful cells and blood-borne molecules away from the brain. In neurological diseases such as multiple sclerosis, the BBB is breached, and inflammatory mediators and cells gain access to the brain and contribute to disease pathology. Alvarez et al. (see the Perspective by Engelhardt) now demonstrate that Sonic hedgehog (Shh) signaling promotes BBB integrity. Pharmacological inhibition of Shh signaling or genetic ablation of Shh signaling in endothelial cells increased BBB permeability in mice. In a mouse model of multiple sclerosis, blockade of Shh signaling increased disease severity. Inflammation promoted Shh signaling, and expression of Shh signaling mediators was elevated in multiple sclerosis lesions.
J. I. Alvarez, A. Dodelet-Devillers, H. Kebir, I. Ifergan, P. J. Fabre, S. Terouz, M. Sabbagh, K. Wosik, L. Bourbonnière, M. Bernard, J. van Horssen, H. E. de Vries, F. Charron, A. Prat, The Hedgehog pathway promotes blood-brain barrier integrity and CNS immune quiescence. Science 334, 1727–1731 (2011). [Abstract] [Full Text]
Citation: K. L. Mueller, Hedgehogs Man the Gate. Sci. Signal. 5, ec6 (2012).
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