ReviewThe American journal of pathology2021
Notch3 Signaling and Aggregation as Targets for the Treatment of CADASIL and Other NOTCH3-Associated Small-Vessel Diseases.
Review in The American journal of pathology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Age-dependent vascular and neurological characteristics of CADASIL are recapitulated in Notch3 mutant zebrafish, implicating a role for type IV collagen in disease progression.Acta neuropathologica communications · 2026Article
- Signaling pathways and molecular mechanisms involved in the onset and progression of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL); a focus on Notch3 signaling.The journal of headache and pain · 2025Review
- Genomic analysis of 11,555 probands identifies 60 dominant congenital heart disease genes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A CADASIL NOTCH3 mutation leads to clonal hematopoiesis and expansion of Dnmt3a-R878H hematopoietic clones.Leukemia · 2025Article
- Mechanistic advances in factors influencing phenotypic variability in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: a review.Frontiers in neurology · 2025Review
- A Search for New Biological Pathways in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy by Proteomic Research.Journal of clinical medicine · 2024Article
- Epidermal Growth Factor Receptors in Vascular Endothelial Cells Contribute to Functional Hyperemia in the Brain.International journal of molecular sciences · 2023Article
- Article
- The emerging role of the HTRA1 protease in brain microvascular disease.Frontiers in dementia · 2023Review
- Evidence of beta amyloid independent small vessel disease in familial Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2022Article
- Genetic spectrum of NOTCH3 and clinical phenotype of CADASIL patients in different populations.CNS neuroscience & therapeutics · 2022Article
- Effects of different regional cerebral blood flow on white matter hyperintensity in CADASIL patients.Journal of biomedical research · 2022Article
- Notch Signaling in Vascular Endothelial and Mural Cell Communications.Cold Spring Harbor perspectives in medicine · 2022Article
- Early-Onset Vascular Leukoencephalopathy Caused by Bi-Allelic NOTCH3 Variants.Neuropediatrics · 2022Article
- Article
- The neurovascular unit in leukodystrophies: towards solving the puzzle.Fluids and barriers of the CNS · 2022Review
- Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in the NOTCH3 gene can lead to small-vessel disease in humans, including the well-characterized cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a condition caused by NOTCH3 mutations altering the number of cysteine residues in the extracellular domain of Notch3. Growing evidence indicates that other types of mutations in NOTCH3, including cysteine-sparing missense mutations or frameshift and premature stop codons, can lead to small-vessel disease phenotypes of variable severity or penetrance. There are currently no disease-modifying therapies for small-vessel disease, including those associated with NOTCH3 mutations. A deeper understanding of underlying molecular mechanisms and clearly defined targets are needed to promote the development of therapies. This review discusses two key pathophysiological mechanisms believed to contribute to the emergence and progression of small-vessel disease associated with NOTCH3 mutations: abnormal Notch3 aggregation and aberrant Notch3 signaling. This review offers a summary of the literature supporting and challenging the relevance of these mechanisms, together with an overview of available preclinical experiments derived from these mechanisms. It highlights knowledge gaps and future research directions. In view of recent evidence demonstrating the relatively high frequency of NOTCH3 mutations in the population, and their potential role in promoting small-vessel disease, progress in the development of therapies for NOTCH3-associated small-vessel disease is urgently needed.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.