Molecular Basis for Vascular Abnormalities of the Brain

The Notch signaling pathway plays a key role in the development and maturation of most vertebrate organs. Disruption of this pathway has been associated with human disease, including Alagille syndrome (a multiorgan system disease associated with liver pathology and congenital heart defects), associated with Notch2, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, associated with Notch3. Evidence in animal models suggests a role for the Notch signaling pathway in the development of vascular malformations, but its role in human vascular pathology has not been established. To determine whether this pathway is involved in brain arteriovenous malformations (AVMs), researchers performed immunohistoch…