Neuronal membranes can enhance or prevent the formation of Abeta oligomers, the neurotoxic species implicated in Alzheimer’s disease. However, the relation between the membrane composition and its effect on Abeta oligomerisation remains unclear. The core of this project is to unravel the molecular mechanism of individual lipids in which they influence Abeta behavior and can prevent its oligomerisation. We will focus on the role of gangliosides (sialic acid-containing glycosphingolipids), which have an important role in brain development, regeneration, and progression of Alzheimer’s disease. We recently showed that Abeta oligomerisation can be prevented by the physiological concentration of one such lipid, GM1. Using state-of-the-art molecular dynamics simulation with advanced sampling techniques and single-molecule fluorescence microscopy and spectroscopy we will investigate other neuronal gangliosides and provide the understanding of their interaction with Abeta peptides at atomistic level. Such information can be used for the risks diagnostics or suggestion of new treatment strategies targeted on nutrition or metabolism of gangliosides.

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