Newswise — One distinguishing trait of Alzheimer's disease is the accumulation of amyloid-β protein, which aggregates to construct plaques within the brain. This protein is generated by an enzyme located in cell membranes. Prof. Harald Steiner and Dr. Edgar Dawkins, leading a team at LMU's Biomedical Center Munich, have demonstrated that the thickness of the membrane affects the production of amyloid-β.
Cellular membranes are composed of lipid bilayers, which can be thickened by the addition of more lipids externally, leading to changes in their characteristics. Previous research conducted by Steiner's group had already revealed in model systems without cells that such alterations can influence the production of amyloid-β. This occurs because the γ-secretase, the primary enzyme responsible for generating amyloid-β, is positioned within the membrane.
Remodeling in the cell membrane alters enzyme activit
The scientists have now established that these basic mechanisms are also relevant in actual cells. For this purpose, they initially devised techniques for altering the characteristics of live cell membranes within cell cultures. As a result, they were able to confirm that the inclusion of a long-chain fatty acid, a fundamental constituent of lipids, caused modifications in the cellular membranes. This adjustment in the membrane's composition also brought about alterations in the function of the γ-secretase.
The impact of this on the generation of amyloid-β was found to be heterogeneous: "Despite our objective of diminishing the production of amyloid-β, we discovered that lipid treatments exhibit intricate consequences on this protein's generation in biological settings," Dawkins commented. "Depending on the cellular genetic makeup, we could decrease or elevate the levels of amyloid-β."
In the long run, the researchers envision their findings providing fresh impetus for developing lipid-based therapies for Alzheimer's disease. "Our investigation includes crucial factors in this regard, which scientists should take into account when appraising possible lipid-based interventions," Steiner remarked. However, he stressed that the practical application of such therapies is still a long way off in the future.
RSS