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Updated: Jun 3, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
04:01

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics

Published on: March 15, 2024

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JAG1/Notch Pathway Inhibition Induces Ferroptosis and Promotes Cataractogenesis

Yan Ni1,2, Liangping Liu1,2, Fanying Jiang1,2

  • 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China.

International Journal of Molecular Sciences
|January 11, 2025
PubMed

Insights

Downregulation of Notch signaling promotes ferroptosis in lens epithelial cells, contributing to age-related cataracts. Enhancing Notch signaling may offer a therapeutic strategy for cataracts by protecting against cell death.

Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Cell Biology

Background:

  • Age-related cataracts (ARCs) are a leading cause of visual impairment globally.
  • The molecular mechanisms driving ARC pathogenesis, especially involving cell death pathways, remain incompletely understood.
  • The Notch signaling pathway's role in degenerative diseases suggests potential involvement in ARCs.

Purpose of the Study:

  • To investigate the role of Notch signaling in regulating ferroptosis in lens epithelial cells (LECs).
  • To determine the impact of Notch signaling on age-related cataract progression.
  • To elucidate the molecular link between Notch signaling, ferroptosis, and ARC development.

Main Methods:

  • RNA sequencing of anterior lens capsule samples from ARC patients.
  • Analysis of Notch1 expression and ferroptosis markers in relation to age.
  • In vitro experiments manipulating Notch signaling in LECs to assess ferroptosis markers (FTH1, p53, Nrf2, GPX4, SLC7A11).

Main Results:

  • ARC patients showed downregulated Notch signaling and upregulated ferroptosis markers, with an age-dependent trend.
  • Upregulating Notch signaling in vitro reduced ferroptosis by decreasing FTH1/p53 and increasing Nrf2/GPX4/SLC7A11.
  • Inhibiting Notch signaling exacerbated ferroptosis, indicated by reduced Nrf2/GPX4/SLC7A11.

Conclusions:

  • Downregulation of Notch signaling promotes ferroptosis in LECs by impairing the Nrf2/GPX4 antioxidant pathway.
  • This Notch signaling-mediated ferroptosis contributes to the development of age-related cataracts.
  • The Notch signaling pathway represents a potential therapeutic target for preventing or treating ARCs.
Keywords:
Notchage-related cataractferroptosislens epithelial cells

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