Tags: mice | switch | off | brain | death

Scientists 'Switch Off' Brain Cell Death in Mice

Sunday, 06 May 2012 04:57 PM

 

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Scientists have figured out how to stop brain cell death in mice with brain disease and say their discovery deepens understanding of the mechanisms of human neurodegenerative diseases such as Alzheimer's and Parkinson's.

British researchers writing in the journal Nature said they had found a major pathway leading to brain cell death in mice with prion disease, the mouse equivalent of Creutzfeld-Jacob Disease (CJD).

They then worked out how to block it, and were able to prevent brain cells from dying, helping the mice live longer.

The finding, described by one expert as "a major breakthrough in understanding what kills neurons," points to a common mechanism by which brain diseases such as Alzheimer's, Parkinson's, and CJD damage the nerve cells.

In neurodegenerative diseases, proteins "mis-fold" in various ways, leading to a buildup of misshapen proteins, the researchers explained in the study.

These misshapen proteins form the plaques found in the brains of patients with Alzheimer's and the Lewy bodies found in Parkinson's disease.

"What's exciting is the emergence of a common mechanism of brain cell death, across a range of different neurodegenerative disorders, activated by the different mis-folded proteins in each disease," said Giovanna Mallucci, who led the research at the University of Leicester's toxicology unit.

"The fact that in mice with prion disease we were able to manipulate this mechanism and protect the brain cells means we may have a way forward in how we treat other disorders," she said in a statement about the work.

An estimated 18 million people worldwide suffer from Alzheimer's, and Parkinson's is thought to affect around one in 100 people over the age of 60. In these diseases, neurons in the brain die, destroying the brain from the inside.

But why the neurons die has remained an unsolved mystery, presenting an obstacle to developing effective treatments and to being able to diagnose the illnesses at early stages when medicines might work better.

Mallucci's team found that the build up of mis-folded proteins in the brains of mice with prion disease activated a natural defence mechanism in cells, which switches off the production of new proteins.

This would normally switch back on again, the researchers explained, but in these ill mice the continued build-up of misshapen proteins keeps the switch turned off. This is the trigger point leading to brain cell death, because key proteins essential for cell survival are not made.

By injecting a protein that blocks the "off" switch, the scientists were able to restore the production of the survival proteins and halt the neurodegeneration.

They found the brain cells were protected, protein levels were restored and synaptic transmission — the way brain cells signal to each other — was re-established. The mice also lived longer, even though only a very small part of their brains had been treated.

Eric Karran, director of research at the charity Alzheimer's Research UK, said while the research was still at an early stage, the results were exciting.

"While neurodegenerative diseases can have many different triggers, this study suggests that they may act through a common mechanism to damage nerve cells. The findings present the appealing concept that one treatment could have benefits for a range of different diseases," he said.

Roger Morris, a professor of molecular neurobiology at King's College London who was not involved in the work, said the finding was "a major breakthrough in understanding what kills neurons in neurodegenerative disease".

"There are good reasons for believing this response, identified with prion disease, applies also to Alzheimer's and other neurodegenerative diseases," he said.

© 2014 Thomson/Reuters. All rights reserved.

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