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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.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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Tissue Transplantation01:24

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Tissue transplantation is a significant medical procedure involving the transfer of cells, tissues, or organs from a donor to a recipient, with the primary aim of restoring lost functions. This procedure is crucial in treating a broad spectrum of diseases, including kidney diseases, liver failure, heart disease, and certain types of cancers.
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Targeting the Notch Pathway to Prevent Rejection.

J Chung1,2, L V Riella3,4, I Maillard5,6,7

  • 1Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI.

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
|April 3, 2016
PubMed
Summary
This summary is machine-generated.

Targeting Notch signaling, a key pathway in immune responses, offers a promising new strategy to prevent organ transplant rejection. Inhibiting Notch ligands effectively reduced immune responses in mouse models, suggesting a novel therapeutic approach.

Keywords:
T cell biologybasic (laboratory) research/sciencebone marrow/hematopoietic stem cell transplantationgraft-versus-host disease (GVHD)heart (allograft) function/dysfunctionheart transplantation/cardiologyimmunosuppression/immune modulationrejection: T cell mediated (TCMR)rejection: antibodymediated (ABMR)translational research/science

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Area of Science:

  • Immunology
  • Cellular signaling
  • Transplantation immunology

Background:

  • Immune rejection involves complex cellular and humoral mechanisms.
  • Current immunosuppression therapies have significant side effects and limited efficacy.
  • Notch signaling is crucial for T cell development and immune response regulation.

Purpose of the Study:

  • To review the role of Notch signaling in allograft rejection.
  • To elucidate the mechanism by which Notch signaling promotes T cell pathogenicity.
  • To propose Notch pathway targeting as a novel therapeutic strategy for preventing transplant rejection.

Main Methods:

  • Review of current literature on Notch signaling in transplant rejection.
  • Analysis of studies using gain-of-function and loss-of-function approaches.
  • Examination of data from mouse models of transplant rejection and graft-versus-host disease.

Main Results:

  • Notch signaling acts as a central mediator of T cell alloreactivity.
  • Short-term inhibition of Notch ligands yielded long-lasting protective effects in allograft models.
  • Blockade of Delta-like Notch ligands reduced both cellular and humoral rejection in a heart allograft model.

Conclusions:

  • Notch signaling promotes T cell pathogenicity and allograft damage.
  • Targeting the Notch pathway presents a potential new therapeutic avenue for preventing allograft rejection.
  • Further research into Notch pathway modulation could lead to improved transplant outcomes.