Alzheimer's breakthrough as molecule to stop 'toxic chain reaction' in brain discovered

Scientists have discovered a way to stop a key stage in the development of Alzheimer's, which could help break the "toxic chain reaction" that leads to brain cell death in sufferers.

Researchers at the University of Cambridge have said they have identified a "molecular chaperone" that can block the progression of Alzheimer's, raising hope that more molecules like this could be found in the future.

They also note that finding these new molecules could be fairly straightforward, as they now know what they are looking for.

The molecule discovered – Brichos – sticks to threads of malfunctioning proteins called amyloid fibrils, a hallmark of the disease. Brichos stops the threads from contacting other proteins, which helps to avoid toxic clusters that allows the disease to proliferate in the brain.

Published in the journal Nature Structural & Molecular Biology, the scientists say this stage of the disease is one of the most critical, and finding a molecule that stops it occurring is a step closer to finding a treatment for the disease.

Lead author Samuel Cohen said: "A great deal of work in this field has gone into understanding which microscopic processes are important in the development of Alzheimer's disease; now we are now starting to reap the rewards of this hard work. Our study shows, for the first time, one of these critical processes being specifically inhibited, and reveals that by doing so we can prevent the toxic effects of protein aggregation that are associated with this terrible condition."

Alzheimer's develops when naturally occurring protein molecules fold into the wrong shape and stick together to create amyloid fibrils.

After amyloid fibrils first form, they then help other proteins that come into contact with them misfold too and then make small clusters that are highly toxic to nerve cells – a critical step believed to be responsible for the effects of the disease.

This stage sets off a toxic chain reaction where more amyloid fibrils are formed.

However, if scientists can intervene at this point, the disease could be slowed considerably, while also leading to far less devastating effects.

"Working closely with our collaborators in Sweden - who had developed ground-breaking experimental methods to monitor the process - we were able to identify a molecule that produced exactly the results that we were hoping to see in experiments," Cohen said.

Researchers then carried out further tests in mice and confirmed that Brichos suppressed the chain reaction.

The team now plans to look for other molecules that could have a similar effect on the disease. "It may not actually be too difficult to find other molecules that do this, it's just that it hasn't been clear what to look for until recently," Cohen said.