CADASIL: a critical look at a Notch disease.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a catastrophic late-onset syndrome which manifests itself mainly as a central nervous system degenerative disorder. CADASIL has been associated with mutations in the Notch 3 receptor which appear to cause, mainly, vascular abnormalities. Although more than a decade has passed since Notch 3 mutations were linked with this disease, we still do not have a good grasp on the molecular mechanisms underlying the CADASIL-associated Notch 3 receptor malfunction, nor do we understand many aspects of the CADASIL pathobiology. In this review, we discuss the CADASIL-related literature and attempt to evaluate the various experimental systems and approaches used to address what seems to be a paradigm for studying the pathobiology and genetics of vascular cognitive impairment.
Louvi
Angeliki
A
Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Arboleda-Velasquez
Joseph F
JF
Artavanis-Tsakonas
Spyros
S
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D046589:CADASIL / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000502:physiology; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology
C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch