Modulation of cell membrane influences formation of amyloid-β, finds research

Including long-chain fatty acids can thicken cell membranes and alter the exercise of a key enzyme, as LMU scientists have demonstrated in cell cultures.

A attribute function of Alzheimer’s illness are deposits of the amyloid-β protein, which clumps collectively to kind plaques within the mind. The amyloid-β protein is produced by an enzyme which resides in mobile membranes. A group lead by Prof. Harald Steiner and Dr. Edgar Dawkins from the Biomedical Middle Munich at LMU has now proven that the manufacturing of amyloid-β is influenced by the membrane thickness.

Mobile membranes encompass lipid bilayers. By externally including additional lipids, they are often thickened, which alters their properties. In earlier research, Steiner’s group had already demonstrated in cell-free mannequin programs that such modifications have an effect on the manufacturing of amyloid-β. This impact arises as a result of the important thing enzyme for the manufacturing of amyloid-β, the so-called γ-secretase, is localized contained in the membrane.

Transforming within the cell membrane alters enzyme exercise

Now the researchers have demonstrated that these elementary mechanisms additionally apply in cells. To this finish, they began out by growing strategies for modifying the properties of dwelling cell membranes in cell cultures. On this method, they have been in a position to present that the addition of a long-chain fatty acid—a constructing block of the lipids—did in truth result in transforming within the cell membranes. This modulation of the membrane composition was additionally related to modifications within the exercise of the γ-secretase.

The best way wherein this influenced the manufacturing of amyloid-β proved to be non-uniform: “Though our objective was to suppress the manufacturing of amyloid-β, we ascertained that the lipid therapies have complicated results on the manufacturing of this protein in organic programs,” stories Dawkins. “Relying on the genetic background of the cells we used, we have been in a position to scale back or enhance the portions of amyloid-β.”

Lengthy-term, the scientists see the potential of their outcomes for delivering new impetuses to lipid-based remedy methods for Alzheimer’s illness. “Our research accommodates vital concerns on this regard, which researchers ought to look into when evaluating potential lipid-based approaches,” says Steiner, though he emphasizes that their sensible implementation stays far off sooner or later.

The findings are printed within the Journal of Organic Chemistry.