CADASIL: A NOTCH3-associated cerebral small vessel disease

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cerebral small vessel disease (CSVD), pathologically characterized by a non-atherosclerotic and non-amyloid diffuse angiopathy primarily involving small to m...

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Main Authors: Lamei Yuan, Xiangyu Chen, Joseph Jankovic, Hao Deng
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Journal of Advanced Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S2090123224000018
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author Lamei Yuan
Xiangyu Chen
Joseph Jankovic
Hao Deng
author_facet Lamei Yuan
Xiangyu Chen
Joseph Jankovic
Hao Deng
author_sort Lamei Yuan
collection DOAJ
description Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cerebral small vessel disease (CSVD), pathologically characterized by a non-atherosclerotic and non-amyloid diffuse angiopathy primarily involving small to medium-sized penetrating arteries and leptomeningeal arteries. In 1996, mutation in the notch receptor 3 gene (NOTCH3) was identified as the cause of CADASIL. However, since that time other genetic CSVDs have been described, including the HtrA serine peptidase 1 gene-associated CSVD and the cathepsin A gene-associated CSVD, that clinically mimic the original phenotype. Though NOTCH3-associated CSVD is now a well-recognized hereditary disorder and the number of studies investigating this disease is increasing, the role of NOTCH3 in the pathogenesis of CADASIL remains elusive. Aim of review: This review aims to provide insights into the pathogenesis and the diagnosis of hereditary CSVDs, as well as personalized therapy, predictive approach, and targeted prevention. In this review, we summarize the current progress in CADASIL, including the clinical, neuroimaging, pathological, genetic, diagnostic, and therapeutic aspects, as well as differential diagnosis, in which the role of NOTCH3 mutations is highlighted. Key scientific concepts of review: In this review, CADASIL is revisited as a NOTCH3-associated CSVD along with other hereditary CSVDs.
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spelling doaj-art-e523ce5752c44525a7b283e2b0a82d162025-08-20T02:21:07ZengElsevierJournal of Advanced Research2090-12322024-12-016622323510.1016/j.jare.2024.01.001CADASIL: A NOTCH3-associated cerebral small vessel diseaseLamei Yuan0Xiangyu Chen1Joseph Jankovic2Hao Deng3Health Management Center, the Third Xiangya Hospital, Central South University, Changsha, China; Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, China; Disease Genome Research Center, Central South University, Changsha, China; Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, ChinaCenter for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, China; Disease Genome Research Center, Central South University, Changsha, China; Department of Pathology, Changsha Maternal and Child Health Care Hospital, Changsha, ChinaParkinson’s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, USAHealth Management Center, the Third Xiangya Hospital, Central South University, Changsha, China; Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, China; Disease Genome Research Center, Central South University, Changsha, China; Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China; Corresponding author at: The Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha, Hunan 410013, China.Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cerebral small vessel disease (CSVD), pathologically characterized by a non-atherosclerotic and non-amyloid diffuse angiopathy primarily involving small to medium-sized penetrating arteries and leptomeningeal arteries. In 1996, mutation in the notch receptor 3 gene (NOTCH3) was identified as the cause of CADASIL. However, since that time other genetic CSVDs have been described, including the HtrA serine peptidase 1 gene-associated CSVD and the cathepsin A gene-associated CSVD, that clinically mimic the original phenotype. Though NOTCH3-associated CSVD is now a well-recognized hereditary disorder and the number of studies investigating this disease is increasing, the role of NOTCH3 in the pathogenesis of CADASIL remains elusive. Aim of review: This review aims to provide insights into the pathogenesis and the diagnosis of hereditary CSVDs, as well as personalized therapy, predictive approach, and targeted prevention. In this review, we summarize the current progress in CADASIL, including the clinical, neuroimaging, pathological, genetic, diagnostic, and therapeutic aspects, as well as differential diagnosis, in which the role of NOTCH3 mutations is highlighted. Key scientific concepts of review: In this review, CADASIL is revisited as a NOTCH3-associated CSVD along with other hereditary CSVDs.http://www.sciencedirect.com/science/article/pii/S2090123224000018CADASILHereditary cerebral small vessel diseaseNOTCH3Predictive approachTargeted prevention
spellingShingle Lamei Yuan
Xiangyu Chen
Joseph Jankovic
Hao Deng
CADASIL: A NOTCH3-associated cerebral small vessel disease
Journal of Advanced Research
CADASIL
Hereditary cerebral small vessel disease
NOTCH3
Predictive approach
Targeted prevention
title CADASIL: A NOTCH3-associated cerebral small vessel disease
title_full CADASIL: A NOTCH3-associated cerebral small vessel disease
title_fullStr CADASIL: A NOTCH3-associated cerebral small vessel disease
title_full_unstemmed CADASIL: A NOTCH3-associated cerebral small vessel disease
title_short CADASIL: A NOTCH3-associated cerebral small vessel disease
title_sort cadasil a notch3 associated cerebral small vessel disease
topic CADASIL
Hereditary cerebral small vessel disease
NOTCH3
Predictive approach
Targeted prevention
url http://www.sciencedirect.com/science/article/pii/S2090123224000018
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AT xiangyuchen cadasilanotch3associatedcerebralsmallvesseldisease
AT josephjankovic cadasilanotch3associatedcerebralsmallvesseldisease
AT haodeng cadasilanotch3associatedcerebralsmallvesseldisease