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
Abstract Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal-dominantly inherited cerebral small-vessel disease (SVD). CADASIL has diverse clinical features such as migraine with aura, dementia, and recurrent strokes, and is caused by...
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| Language: | English |
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BMC
2025-04-01
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| Series: | The Journal of Headache and Pain |
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| Online Access: | https://doi.org/10.1186/s10194-025-02025-z |
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| author | Parasta Heidari Motahareh Taghizadeh Omid Vakili |
| author_facet | Parasta Heidari Motahareh Taghizadeh Omid Vakili |
| author_sort | Parasta Heidari |
| collection | DOAJ |
| description | Abstract Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal-dominantly inherited cerebral small-vessel disease (SVD). CADASIL has diverse clinical features such as migraine with aura, dementia, and recurrent strokes, and is caused by a pathogenic mutation in the NOTCH3 gene which encodes a transmembrane receptor found in smooth muscle cells of small arteries and pericytes of brain capillaries. Pathogenic mutations alter the number of cysteine residues in the extracellular domain of NOTCH3, leading to the abnormal accumulation of granular osmiophilic material in the vessels of affected individuals. In addition, potential signaling pathways, such as transforming growth factor beta (TGF-β), may be involved in pathogenesis of the disease. This review aims to elucidate these mechanisms, particularly NOTCH3, in the context of CADASIL pathogenesis, providing insight into the role of NOTCH3 signaling and discussing the significance of these pathways for potential future therapeutic interventions in CADASIL patients. |
| format | Article |
| id | doaj-art-64cbb7172e7c41c5a6ab443170835d49 |
| institution | OA Journals |
| issn | 1129-2377 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | The Journal of Headache and Pain |
| spelling | doaj-art-64cbb7172e7c41c5a6ab443170835d492025-08-20T02:10:50ZengBMCThe Journal of Headache and Pain1129-23772025-04-0126112610.1186/s10194-025-02025-zSignaling 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 signalingParasta Heidari0Motahareh Taghizadeh1Omid Vakili2Center for Genomics and Personalized Health, Queensland University of TechnologyDepartment of Clinical Biochemistry, School of Medicine, Shiraz University of Medical SciencesDepartment of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical SciencesAbstract Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal-dominantly inherited cerebral small-vessel disease (SVD). CADASIL has diverse clinical features such as migraine with aura, dementia, and recurrent strokes, and is caused by a pathogenic mutation in the NOTCH3 gene which encodes a transmembrane receptor found in smooth muscle cells of small arteries and pericytes of brain capillaries. Pathogenic mutations alter the number of cysteine residues in the extracellular domain of NOTCH3, leading to the abnormal accumulation of granular osmiophilic material in the vessels of affected individuals. In addition, potential signaling pathways, such as transforming growth factor beta (TGF-β), may be involved in pathogenesis of the disease. This review aims to elucidate these mechanisms, particularly NOTCH3, in the context of CADASIL pathogenesis, providing insight into the role of NOTCH3 signaling and discussing the significance of these pathways for potential future therapeutic interventions in CADASIL patients.https://doi.org/10.1186/s10194-025-02025-zCADASILNOTCH3Signal transductionGeneticsCerebral small vessel disease |
| spellingShingle | Parasta Heidari Motahareh Taghizadeh Omid Vakili 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 CADASIL NOTCH3 Signal transduction Genetics Cerebral small vessel disease |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | CADASIL NOTCH3 Signal transduction Genetics Cerebral small vessel disease |
| url | https://doi.org/10.1186/s10194-025-02025-z |
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