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Review
. 2020 Mar 13:11:321.
doi: 10.3389/fphar.2020.00321. eCollection 2020.

Pathophysiological Mechanisms and Potential Therapeutic Targets in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL)

Martina Locatelli  1 , Alessandro Padovani  1 , Alessandro Pezzini  1
Affiliations
Review

Pathophysiological Mechanisms and Potential Therapeutic Targets in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL)

Martina Locatelli et al. Front Pharmacol. .

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), is a hereditary small-vessels angiopathy caused by mutations in the NOTCH 3 gene, located on chromosome 19, usually affecting middle-ages adults, whose clinical manifestations include migraine with aura, recurrent strokes, mood disorders, and cognitive impairment leading to dementia and disability. In this review, we provide an overview of the current knowledge on the pathogenic mechanisms underlying the disease, focus on the corresponding therapeutic targets, and discuss the most promising treatment strategies currently under investigations. The hypothesis that CADASIL is an appropriate model to explore the pathogenesis of sporadic cerebral small vessel disease is also reviewed.

Keywords: CADASIL; ischemic; migraine with aura; small-vessel disease; stroke; vascular cognitive impairment.

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Figures

Figure 1
Figure 1
Brain magnetic resonance imaging (MRI) T2 showing extensive leukoencephalopathy with marked involvement of anterior temporal lobes (A) and external capsule (B).
Figure 2
Figure 2
Notch 3 receptor structure. WT, wild type; EGFR, epidermal growth factor-like repeats; LNR, Lin12 repeats.
Figure 3
Figure 3
Wild type Notch3. ICD, intracellular domain.
See this image and copyright information in PMC

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