Public Release: 

Progress toward a more targeted treatment of Alzheimer's disease

VIB (the Flanders Institute for Biotechnology)

Leuven, Belgium - Leuven - Scientists from the Flanders Interuniversity Institute for Biotechnology (VIB) connected with the Catholic University of Leuven have shed a little more light on Alzheimer's disease. They've gone deeply into the operation of γ-secretase, a crucial factor in the origin of the disease. Their research has revealed that the action of γ-secretase is not homogeneous - as previously assumed - but quite differentiated. This discovery opens up perspectives for new medicines that will have fewer undesired side effects than current medicines do.

Alzheimer's disease
Alzheimer's disease, a degenerative disease that gradually and progressively destroys brain cells, affects between 50% and 70% of all cases of dementia and is therefore the major form of dementia. About 100,000 people suffer from this disease in Belgium. The damage caused to memory and mental functioning makes it one of today's most frightening syndromes. In particular, the first realization of the loss of any sense of reality is extremely difficult to accept. So, science continues to search feverishly for ways to treat the disease.

The role of γ-secretase
Alzheimer's disease involves a kind of plaque that forms in the brain cells. Several years ago, Bart De Strooper and other researchers deciphered the process by which the plaques originate. A major role in this process is played by γ-secretase, an enzyme that cuts proteins in a particular place. Sometimes the γ-secretase cleavage goes wrong, causing the creation of a by-product that sticks together and precipitates - thus forming the plaque. In their quest for new medicines, scientists are investigating this key role of ?-secretase to try to find substances that are able to block the formation of plaques. A thorough understanding of γ-secretase is therefore critical.

Diverse tissue-specific activity
γ-secretase is divided into several entities, but until now scientists have assumed that the complex acts as a homogeneous unit. However, Lutgarde Serneels and Bart De Strooper now show that γ-secretase's various sub-units exhibit very diverse, tissue-specific activity. They have deduced this from research in which they inactivate one or more sub-units in mice. The effect of this inactivation turns out to be very specific for each sub-unit: in one instance, the mice embryos were not viable; but the inactivation of another sub-unit led to adult mice in which the activity of γ-secretase was significantly reduced.

On the road to a more specific treatment
This opens up new possibilities for the development of medicines that focus on the inactivation of γ-secretase. Because current methods prevent the action of the entire complex, they also cause a lot of undesired side effects. The findings of the Leuven researchers should make it possible to develop medicines that are targeted on a single sub-unit and thereby have a much more specific action.

'You will probably never be able to give people their memory back," says Bart De Strooper. "So, the main purpose of a medicine will be to salvage as many brain cells as you can by halting the progress of the disease in the areas of the brain where it has already developed, and by preventing plaque from forming in the parts of the brain they have not yet affected."


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