A study discovered that changing the cell membrane influences the production of amyloid-β.

LMU researchers have demonstrated in cell cultures that the addition of long-chain fatty acids can alter the activity of a crucial enzyme and thicken cell membranes.

Deposits of the protein amyloid, which clumps together to form plaques in the brain, are a hallmark of Alzheimer’s disease. The amyloid protein is delivered by a compound that lives in cell layers. Now, a group led by Prof. Harald Steiner and Dr. Edgar Dawkins from the Biomedical Center Munich at LMU has demonstrated that membrane thickness influences the production of amyloid.

Lipid bilayers make up cell membranes. They can be thickened externally by adding additional lipids, which alters their properties. Steiner’s group had previously demonstrated in cell-free model systems that such modifications affect the production of amyloid in previous studies. This impact emerges in light of the fact that the critical chemical for the creation of amyloid-, the supposed -secretase, is limited inside the layer.

“In this regard, our study contains important considerations that researchers should consider when evaluating potential lipid-based approaches,”

Prof. Harald Steiner , from the Biomedical Center Munich at LMU

Enzyme activity is altered by cell membrane remodeling.

The activity of enzymes changes when the cell membrane is remodelled, and now the researchers have shown that these fundamental mechanisms work in cells as well. To this end, they began by creating techniques for adjusting the properties of living cell layers in cell societies. Along these lines, they had the option to show that the expansion of a long-chain unsaturated fat — a structure block of the lipids —did, as a matter of fact, lead to remodeling in the cell films. Changes in the activity of the secretase were also linked to this alteration in the composition of the membrane.

There was no consistent pattern to how this affected the production of amyloid. “We ascertained that the lipid treatments have complex effects on the production of this protein in biological systems,” states Dawkins, “even though our goal was to suppress the production of amyloid.” We were able to alter the amount of amyloid depending on the genetic background of the cells we used.

The researchers believe that their findings have the potential to provide new impetus to lipid-based Alzheimer’s disease treatment strategies in the long run. “While he emphasizes that their practical implementation remains far off in the future, our study contains important considerations in this regard that researchers should look into when evaluating potential lipid-based approaches,” Steiner states.

The Journal of Biological Chemistry has published the findings.

More information: Edgar Dawkins et al, Membrane lipid remodeling modulates γ-secretase processivity, Journal of Biological Chemistry (2023). DOI: 10.1016/j.jbc.2023.103027

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