Publication Date
12-1-2024
Journal
Journal of Advanced Research
DOI
10.1016/j.jare.2024.01.001
PMID
38176524
PMCID
PMC11674792
PubMedCentral® Posted Date
1-2-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Humans, CADASIL, Receptor, Notch3, Cerebral Small Vessel Diseases, Mutation, Hereditary cerebral small vessel disease, Predictive approach, Targeted prevention
Abstract
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.