PP1 suppression of Src tyrosine kinases can prevent the neuronal damage in strokes by influencing brain vessel permeability.
The only established treatment for acute ischaemic stroke is thrombolysis, but this is associated with the risk of severe, sometimes life threatening haemorrhage. In the February issue of
Tissue ischaemia results in an overproduction of vascular endothelial growth factor (VEGF), which in turn increases the permeability of blood vessels in the brain. These leaky vessels lead to swelling in the brain and subsequent neuronal damage. A family of tyrosine kinase molecules called the Src kinases links VEGF and increased vascular permeability.
Robert Paul and colleagues show that suppression of Src activity decreases vascular permeability, with mice deficient in Src having decreased infarct volumes and reduced oedema (Nat Med 2001, 7:222-227). Using the drug PP1, which ...