Yoon said that p75 is actually the protein that kills neurons, but it needs proNGF to do so. p75 is a receptor in healthy neurons, it receives signals from outside the cell, translates them, and feeds them to the cell body.
For reasons researchers don't fully understand, neuronal damage causes a dramatic change in p75's behavior. Instead of sending information to the cell body, p75 turns into a receptor that kills the cell but only in the presence of proNGF.
proNGF is a precursor to nerve growth factor (NGF), a molecule that stimulates the growth and survival of certain nerve cells. Normally, proNGF produced inside the cell is broken down into two substances, one of which is mature NGF, a molecule that gets secreted to help neurons grow and survive.
"But damage to mature neurons somehow blocks the normal production of helpful, mature NGF, and instead proNGF is secreted," Yoon said. "After injury, or during brain diseases like Alzheimer's, proNGF levels skyrocket."
The researchers saw substantial increases in proNGF and p75 in damaged neurons within 24 hours after injury. Levels of p75 peaked three days after injury, as did neuronal death.
The researchers took another group of damaged neurons and treated these cells with an antibody to proNGF. Doing so kept proNGF from interacting with p75, and resulted in a 92 percent survival rate of otherwise damaged neurons.
"The antibody notably reduced the number of neurons that normally die after such injury," Yoon said. "But it's too soon to say if these rescued cells would function normally again after treatment.
"We do know that injury decreased the number of healthy, viable neurons by half," she said. "But the number of intact neurons remained at nearly 100 percent after antibody treatment."
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Contact: Sung Ok Yoon
Yoon.84@osu.edu
614-292-8542
Ohio State University
15-Mar-2004