Nearly 44 million people have Alzheimer’s or a related
dementia and every 66 seconds in the US develops Alzheimer’s disease.
Alzheimer’s or dementia, a chronic impairment of brain functions marked mainly
by memory problems and behavioral changes with a huge impact on patients and
families.
Many multinational pharmaceutical companies have their drug
candidates in clinical trials raising hopes that an effective treatment could
be finally within reach. However, several decades of research, and hundreds of
failed Alzheimer’s disease trials, including recent failure of Eli Lilly’s
solanezumab, we still know very little about this disease and it has no cure.
Now, a team of researchers at Cambridge University could be
one step closer to a cure for Alzheimer's after discovering how a key process
that triggers the disease takes place.
The signature hallmark of the disease - the most common
form of dementia - is the build-up of protein plaques in the brain.
Scientists believe they have identified the mechanism by
which these plaques accumulate.
But the real breakthrough is that they believe they can
show it is possible to control this process - raising hopes of ultimately
stopping it altogether.
The central dogma of our life revolves around the ability
of DNA to replicate, transcribe and translate. But all of three needs
supporting machineries. This has been the basis of almost all the research.
There are proteins that could replicate without the help of additional
machineries, such as the small, disease-causing protein fibers, fibrils that
are involved in neurodegenerative disorders, including Alzheimer's and
Parkinson's.
The basic idea that was proposed was:
These fibrils, known as amyloids, become intertwined and
entangled with each other, causing the so-called 'plaques' that are found in
the brains of Alzheimer's patients. Spontaneous formation of the first amyloid
fibrils is very slow and takes several years which could explain why Alzheimer's
is usually a disease that affects people in their old age. However, once the
first fibrils are formed, they begin to replicate and spread much more rapidly
by themselves, making the disease very difficult to control.
Despite its importance, the fundamental mechanism of how
protein fibrils can self-replicate without any additional machinery is not well
understood.
In a study published in the journal Nature Physics, a team
led by researchers from the Department of Chemistry at the University of
Cambridge used a combination of computer simulations and laboratory experiments
to identify the necessary requirements for the self-replication of protein
fibrils.
The replication of fibrils was controlled by a common
physical mechanism: the build-up of
healthy proteins on the surface of existing fibrils.
The researchers used a molecule known as amyloid-beta,
which forms the main component of the amyloid plaques found in the brains of
Alzheimer's patients. They found a relationship between the amount of healthy
proteins that are deposited onto the existing fibrils and the rate of the
fibril self-replication. In other words, the greater the build-up of proteins
on the fibril, the faster it self-replicates.
They also showed, as a proof of principle, that by changing
how the healthy proteins interact with the surface of fibrils, it is possible
to control the fibril self-replication.
One of the unfilled goals in nanotechnology is achieving
efficient self-replication in the manufacturing of Nano-materials. The idea of
self-replicating fibrils makes nanotechnology a more interesting field. Andela
ล aric, Ph.D., the study’s first author argued that “If we're able to learn the
design rules from this process, we may be able to achieve this goal”.
The findings are
published in the journal Nature Physics.
