Related Experiment Video

Updated: Oct 7, 2025

Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel
08:29

Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel

Published on: May 14, 2018

10.1K

cADPR induced calcium influx mediates axonal degeneration caused by paclitaxel

Ahmet Höke1

  • 1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.

The Journal of Cell Biology
|January 12, 2022
PubMed

Insights

Chemotherapy drug paclitaxel triggers axonal degeneration by activating Sarm1, leading to the breakdown product cyclic ADP-ribose (cADPR). This cADPR then causes calcium influx into axons, driving degeneration.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Sarm1 activation is known to mediate chemotherapy-induced axonal degeneration.
  • The precise downstream molecular mechanisms following Sarm1 activation remain largely uncharacterized.

Purpose of the Study:

  • To elucidate the downstream signaling pathway by which Sarm1 activation leads to axonal degeneration.
  • To identify the specific molecules involved in paclitaxel-induced neurotoxicity.

Main Methods:

  • Utilized cell culture models and biochemical assays to investigate the role of NAD metabolites.
  • Examined the impact of cADPR on calcium homeostasis within axons.

Main Results:

  • Demonstrated that cyclic ADP-ribose (cADPR), a breakdown product of NAD+, is a key mediator of paclitaxel-induced axonal degeneration.
  • Showcased that cADPR promotes calcium influx into axons, a critical step in the degeneration process.

Conclusions:

  • cADPR acts as a crucial downstream effector of Sarm1 activation in chemotherapy-induced axonal degeneration.
  • Targeting the cADPR-mediated calcium influx pathway may offer therapeutic strategies against neurotoxicity.

More Related Videos

Visualizing Axonal Growth Cone Collapse and Early Amyloid β Effects in Cultured Mouse Neurons06:23

Visualizing Axonal Growth Cone Collapse and Early Amyloid β Effects in Cultured Mouse Neurons

Published on: October 30, 2018

8.1K
Advanced Glycation End-Products Sensitize Human Sensory-Like Neuron Cells to Capsaicin-Induced Calcium Influx06:05

Advanced Glycation End-Products Sensitize Human Sensory-Like Neuron Cells to Capsaicin-Induced Calcium Influx

Published on: May 2, 2025

619

Related Concept Videos

Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.9K
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.2K