Notch signaling and CADASIL.
Notch signaling plays an essential role in vascular development and human vascular diseases. In adults, mutations of the Notch3 gene cause a hereditary vascular degenerative disease known as cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL). CADASIL is characterized by recurrent strokes and cognitive impairment. Over the past decade, the number of CADASIL patients increased significantly with improvements in genetic testing and other diagnostic tools, but the true prevalence of CADASIL is still underestimated, especially in Asia. Basic studies suggest that Notch3 is essential for the development and survival of the vascular smooth muscle cells, but the mechanisms by which Notch3 mutations become pathogenic are still unclear. This article reviews the clinical features and possible pathogenesis of CADASIL. Efforts to improve the diagnostic accuracy and define the role of Notch3 mutation in brain damage and clinical presentations of CADASIL should be continued.
Tang
Sung-Chun
SC
Stroke Center, National Taiwan University Hospital, Taiwan.
Jeng
Jiann-Shing
JS
Lee
Ming-Jen
MJ
Yip
Ping-Keung
PK
D000818:Animals; D046589:CADASIL / Q000150:complications / Q000175:diagnosis / Q000209:etiology*; D003072:Cognition Disorders / Q000209:etiology; D004195:Disease Models, Animal; D006801:Humans; D008279:Magnetic Resonance Imaging; D008881:Migraine Disorders / Q000209:etiology; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D020521:Stroke / Q000209:etiology
C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch