[Pathophysiology of CADASIL disease].
The pathogenic mechanism underlying Cerebral Autosomal Dominant Artheriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) remains elusive although the disease is well characterized at clinical, histological and genetic level. The conservation of the Notch pathway among species allowed the development of several animal and cellular models in order to study it. This review analyzes the reliability of the 7 pathogenic models raised for CADASIL disease: autoimmune origin, mitochondrial dysfunction, loss of Notch3 function, granular osmiophilic material (GOM) toxicity and long term unfolded protein response (UPR) activation. Besides, the relationship between vascular smooth muscle cells (VSMC) degeneration, ischemic lesions and symptoms are discussed. Lastly, some theories are pointed that would explain the exclusiveness of clinical expression to the neural system, being in fact a systemic artheriopathy.
Del Río Espínola
Alberto
A
Laboratorio de Investigación Neurovascular, Departamento de Medicina, Universidad Autónoma de Barcelona, Institut de Recerca, Hospital Vall d'Hebrón Barcelona, España.
Solé
Esther
E
Montaner
Joan
J
D000818:Animals; D002539:Cerebral Arterial Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D056784:Leukoencephalopathies / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000502:physiology
C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch