Researchers at the VIB-KULeuven Centre for Brain & Disease Research have uncovered an important step in the way the brain cells deteriorate during Alzheimer’s Disease.
One of the key indicators of Alzheimer’s is a thing called amyloid plaques, agglomerations of proteins brought together by gamma-secretase, a complex of four proteins.
The Leuven research, supported by the university and the Flemish Institute for Biotechnology (VIB), has discovered how gamma-secretase actually comes together.
Given the interest over the last two decades in gamma-secretase, and its role in Alzheimer’s, the substance has been a target for researchers since it was first discovered.
The discovery amounts to this: gamma-secretase is composed of four proteins. But those four proteins are in fact divided into two pairs of two. At the same time, the underlying proteins can take different forms, so that one gamma-secretase complex is not necessarily the same as the other.
In its different forms, gamma-secretase performs different functions, but as far as Alzheimer’s research is concerned, the process by which the four proteins come together has been of interest.
Professor Wim Annaert has been looking into the question for years. The team worked together with Randy Schekman of the university of Berkeley in California, who won the Nobel Prize for Chemistry in 21o3 for his method.
"By combining his method with high-resolution microscopy, we were able to establish that the four parts of the gamma-secretase complex are put together step-by-step,” Prof. Annaert told he VRT.
“In a first phase, two stable duos are formed, only afterwards – and at a different location in the cell. – both duos are 'clicked together' to form the full active complex."
The key to that process, from the point of view of medicine, is that only four-part structures that are perfect are then released into the system. If there were a way to disrupt the process, the disease could be curtailed, or even prevented.
“And now that we understand the mechanism by which nerve cells produce gamma-secretase, one can look more specifically for such agents,” Prof. Annaert said. This could potentially prevent Alzheimer's by preventing the formation of plaques in the brain, rather than trying to slow down the disease by acting when plaques have already formed.
However the university was keen to point out that an advance in research does not translate directly into an advance in treatment. The institution invites anyone with questions – for example relatives of sufferers – to send their questions to the email address patienteninfo@vib.be.
The study is published in the Journal of Cell Biology.
