s, 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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Contact: Sooike Stoops
VIB, Flanders Interuniversity Institute of Biotechnology
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