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Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
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Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

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Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
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Structure of Cadherins01:25

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The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins”   is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This...
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Cadherins in Tissue Organization01:19

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The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
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Catenins01:23

Catenins

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Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
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Cardiomyopathy III: Hypertrophic Cardiomyopathy01:29

Cardiomyopathy III: Hypertrophic Cardiomyopathy

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Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
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Related Experiment Video

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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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Serum NOTCH3 Extracellular Domain in Patients With CADASIL.

Hyesung Kim1, Yumi Yamamoto2, Young Ree Kim3

  • 1Department of Convergence Biomedical Science, Jeju National University College of Medicine, South Korea.

Neurology. Genetics
|November 3, 2025
PubMed
Summary

Serum N3ECD levels do not reliably diagnose Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). Age-related increases in N3ECD may indicate disease progression in specific genetic variants.

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Area of Science:

  • Neurology
  • Genetics
  • Biomarker Discovery

Background:

  • Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary small vessel disease linked to NOTCH3 gene variants.
  • The extracellular domain of NOTCH3 (N3ECD) is a proposed serum biomarker for CADASIL, but its diagnostic utility is unconfirmed.

Purpose of the Study:

  • To evaluate serum N3ECD levels in CADASIL patients.
  • To assess the potential of N3ECD as a diagnostic or prognostic biomarker for CADASIL.

Main Methods:

  • Serum N3ECD levels were measured using ELISA in two independent CADASIL cohorts (Korean and Japanese).
  • Statistical analyses compared N3ECD levels between CADASIL patients, healthy controls, and ischemic stroke patients, and correlated them with clinical/radiologic features.

Main Results:

  • Serum N3ECD levels did not significantly differ between CADASIL patients and controls or stroke patients.
  • N3ECD levels positively correlated with age in CADASIL patients, particularly in those with specific NOTCH3 variants (p.Arg544Cys and p.Arg75Pro).
  • No significant associations were found between N3ECD levels and MRI markers or clinical outcomes.

Conclusions:

  • Serum N3ECD alone has limited diagnostic value for CADASIL.
  • Age-dependent N3ECD increases in specific variant carriers may reflect disease progression.
  • Further research is needed to clarify N3ECD's role and its potential for monitoring disease progression or treatment response in CADASIL.