NZ scientists find key link in brain disorders

17 August 2010

New Zealand scientists have discovered the workings of a key mechanism of the "cell suicide" that occurs in Alzheimer's disease and other brain disorders.

Auckland University biochemist Associate Professor Tom Brittain said yesterday their findings filled a gap in scientific knowledge which could lead to a drug to treat conditions such as Huntington's, Parkinson's, Alzheimer's and stroke.

"If we understand what it does, we may be able to make a drug which mimics what it does - potentially a treatment, but that's a long, long way off yet."

In collaboration with the University of California, Davis, and funded mainly by the Neurological Foundation of New Zealand, the scientists investigated the role of the protein neuroglobin, which is present in the brain, particularly in nerve cells.

Previous studies have shown that a high level of neuroglobin protects against cell suicide or "apoptosis" caused by lack of oxygen and "amyloid insult", an abnormal protein build-up associated with Alzheimer's and other neurological disorders.

"However, until now, the exact mechanism of neuroglobin's protective action has not been determined," the researchers say in the journal Apoptosis.

They focused on the process that leads quickly to cell death after various kinds of stress, such as lack of oxygen, low nutrient levels, increased calcium levels or the presence of toxic substances.

These events can lead to the rupturing of the mitochondria, the tiny capsule within the cell that makes most of the raw material the cell uses to produce its energy.

When the mitochondria ruptures, it emits a molecule called cytochrome c, which binds to other molecules in the cell to produce a protein called an apoptosome. This helps build an enzyme that degrades and eventually collapses the cell.

Nerve cells can survive damage to the mitochondria if apoptosomes do not form.

Dr Brittain said cell suicide also had benefits. "A number of cancers, particularly brain cancers, increase their concentration of neuroglobin and that's how they protect themselves from being killed."

So the aim would be to produce a small molecule that mimicked neuroglobin but which had a short life span.

"Down the track we could see this as being particularly useful for treating stroke, because in stroke the blood supply stops and the brain cells die over hours to days.

"What we would hope to do is give one dose of this small molecule which would stop that process; the nerve cells wouldn't die and then your body would hopefully clear the small molecule, so you wouldn't have risk of cancer long term."

By Martin Johnston
Friday Aug 6, 2010