2025/04/29 by Parasta Heidari, Motahareh Taghizadeh, Omid Vakili · 1 voice · 1 citation
Medicine · Neuroscience · #Cerebrovascular and genetic disorders #Moyamoya disease diagnosis and treatment #Neurological diseases and metabolism
paper · pdf · doi:10.1186/s10194-025-02025-z
openalex publication_date 2025/04/29 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/29
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. • CADASIL is a rare hereditary cerebral small-vessel disease caused by mutations in NOTCH3 and its associated factors. • Understanding the role of the NOTCH3 signaling pathway may help in understanding that pathomechanisms of CADASIL and its manifestations. • Recognizing the potential involvement of other signaling pathways, including TGF-β, that may contribute to the development or progression of CADASIL is important. • Exploring the roles of these key signaling pathways associated with CADASIL provides a foundation for advancing management and treatment strategies.