Researchers have identified a molecule that can stop an essential stage in the progression of Alzheimer’s disease. The molecule sticks to faulty proteins and prevents them developing toxic clusters in the brain.
Scientist from UK and Swedish recommend their finding will assist the development of drugs that could prevent Alzheimer’s disease development.
They published their findings and its significances in the journal Nature Structural & Molecular Biology.
Led author Dr. Samuel Cohen, states that with research like their own, we are starting to reap the rewards of the substantial work that has been done to maximize our understanding of the microscopic procedures engaged in the progression of Alzheimer’s. He adds:
“Our study reveals, for the initial time, one of these crucial processes being particularly restricted, and shows that by performing so we can stop the toxic effects of protein aggregation that are connected with this horrible condition.”
Many functions in cells are performed by cautiously folded proteins. Folding is an energy-effective way of delivering distant parts of the protein molecule that need to interact are close to each other. Some of these structures are complicated and require the help of housekeeping molecules known as “chaperones.”
A key phase in the progression of Alzheimer’s and other degenerative conditions is the accumulation or “nucleation” of misfolded proteins – well-known as amyloid fibrils – that do not disperse or dissolve away but form toxic clusters and assist the disease propagation in the brain.
The compound that the international team has identified is a chaperone known as Brichos that sticks to threads of amyloid fibrils and prevents them coming into contact with one another, thus stopping the toxic chain reaction.
Brichos interferes with chain reaction that speeds up progression of Alzheimer’s
Earlier work by this team and other investigators recommend there is a another crucial step in the progression of Alzheimer’s disease. As amyloid fibrils start to form, they lead to other proteins to misfold and form small clusters known as oligomers. These are extremely toxic to nerve cells and are considered to be accountable for the harmful effect of Alzheimer’s disease.
This 2nd stage – known as secondary nucleation – is what researchers think sets off the chain reaction that accelerates the development of Alzheimer’s. Without secondary nucleation, single molecules would have to misfold and form clusters devoid of help – a much sluggish and less harmful process.
Thanks to the massive amount of work that has gone on in this area, the team has gathered a wealth of information so they can model what takes place not only as Alzheimer’s progresses, but also what occurs if a step is disturbed or turned off.
The research reveals that Brichos efficiently blocks secondary nucleation and prevents the chain reaction that accelerates Alzheimer’s disease.
In humans, Brichos helps proteins prevent misfolding. Lab assessments revealed that when the chaperone encounters an amyloid fibril, it holds itself to sites on its surface developing a layer that prevents it helping other proteins to misfold and nucleate into toxic oligomers.
Tests in living mice proved that the molecule suppressed the chain reaction from secondary nucleation.
Dr. Cohen states that it may not be challenging to discover other molecules that do this; till recently, it had just been not clear what to look for. He notes:
“A good method now is to search for other compounds that have this same highly targeted effect and to see if these can be applied as the starting point for developing a future treatment.”