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Toxin from brain cells triggers neuron loss in human ALS model
Date:2/6/2014

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In the study, Dr. Przedborski and study co-authors Diane Re, PhD, and Virginia Le Verche, PhD, associate research scientists, removed astrocytes from the brain and spinal cords of six ALS patients shortly after death and placed the cells in petri dishes next to healthy motor neurons. Because motor neurons cannot be removed from human subjects, they had been generated from human embryonic stem cells in the Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, also at CUMC.

Within two weeks, many of the motor neurons had shrunk and their cell membranes had disintegrated; about half of the motor neurons in the dish had died. Astrocytes removed from people who died from causes other than ALS had no effect on the motor neurons. Nor did other types of cells taken from ALS patients.

The researchers confirmed that the cause of the motor neurons' death was a toxin released into the environment by immersing healthy motor neurons in the astrocytes' culture media. The presence of the media, even without astrocytes, killed the motor neurons.

How the Toxin Triggers Motor Neuron Death

The researchers have not yet identified the toxin released by the astrocytes. But they did discover the nature of the neuronal death process triggered by the toxin.The toxin triggers a biochemical cascade in the motor neurons that essentially causes them to undergo a controlled cellular explosion.

Drs. Przedborski, Re, and Le Verche found that they could prevent astrocyte-triggeredmotor neuron death by inhibiting one of the key components of this molecular cascade.

These findings may lead to a way to prevent motor neuron death in patients and potentially prolong life. But the therapeutic potential of such inhibition is far from clear. "For example, we don't know if this would leave patients with living but dysfunctional neurons," Dr. Przedborski said. The researchers are now testing the idea of inhibition in
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Contact: Karin Eskenazi
ket2116@columbia.edu
212-342-0508
Columbia University Medical Center
Source:Eurekalert  

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