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Updated: Sep 19, 2025

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
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Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

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The role of NOTCH3 in CADASIL pathogenesis: insights into novel therapies

Favour Felix-Ilemhenbhio1, Klaudia Kocsy1, Mimoun Azzouz1

  • 1The University Sheffield, Sheffield Institute for Translational Neuroscience, United Kingdom.

Brain Research
|June 2, 2025
PubMed

Insights

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic disorder caused by NOTCH3 gene mutations. This review details its mechanisms and explores potential therapies to restore normal NOTCH3 function.

Area of Science:

  • Neurology
  • Genetics
  • Vascular Biology

Background:

  • Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small-vessel disease.
  • It is characterized by recurrent strokes, cognitive decline, and neurological deficits.
  • NOTCH3 gene mutations impair protein processing, leading to granular osmiophilic material (GOM) accumulation in vessel walls.

Purpose of the Study:

  • To comprehensively analyze the pathophysiological mechanisms of CADASIL.
  • To investigate the impact of NOTCH3 mutations on protein processing and signaling.
  • To explore therapeutic strategies for CADASIL.

Main Methods:

  • Review of existing literature on CADASIL.
  • Analysis of NOTCH3 gene mutations and their effects.
  • Examination of proposed therapeutic approaches.

Main Results:

  • NOTCH3 mutations disrupt protein processing and signaling pathways.
  • This disruption leads to GOM accumulation, causing vascular damage.
  • Current therapeutic strategies aim to restore normal NOTCH3 function.

Conclusions:

  • Understanding NOTCH3's role is crucial for CADASIL pathogenesis.
  • Targeting NOTCH3 processing and signaling offers potential therapeutic avenues.
  • Further research is needed to develop effective CADASIL treatments.

Keywords:
CADASILCerebrovascular diseaseGene therapyNOTCH3StrokeVascular smooth muscle cells (VSMCs)

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