Responsibility of lipid compositions for the amyloid ß assembly induced by ganglioside nanoclusters in mouse synaptosomal membranes

Heterogeneous Ganglioside-Enriched Nanoclusters with Different Densities in Membrane Rafts Detected by a Peptidyl Molecular Probe

“…The d18:1–C18:0 GM1 species of the [M–H] − ion was identified as m/z 1544.9 in which ceramide had a sphingosine of 18 carbons (d, dihydroxy; 1, one double bond) and a stearoyl residue (C18:0) (Figure , Table S4). , The major ceramide components of GM1, isolated from the bovine brain, used in AFM observations were d18:1–C18:0 (52%) and d20:1–C18:0 (48%), as previously reported. , On the other hand, four major gangliosides (GM1, GD1a, GT1b, and GQ1) obtained from PC12 cells were analyzed (Table S5), whereas fucosyl GM1 was not detected . d22:1–C18:0 (d20:1–C20:0) GM1 was the most abundant (71%) followed by shorter d16:1–C18:0 (d18:1–C16:0) and d18:1–C18:0 (18 and 11%, respectively).…”

“…48,49 The major ceramide components of GM1, isolated from the bovine brain, used in AFM observations were d18:1−C18:0 (52%) and d20:1−C18:0 (48%), as previously reported. 1,32 On the other hand, four major gangliosides (GM1, GD1a, GT1b, and GQ1) obtained from PC12 cells were analyzed (Table S5), whereas fucosyl GM1 was not detected. 44 d22:1−C18:0 (d20:1− C20:0) GM1 was the most abundant (71%) followed by shorter d16:1−C18:0 (d18:1−C16:0) and d18:1−C18:0 (18 and 11%, respectively).…”

“…An electrospray ionization/ion trap mass spectrometer (Esquire 3000 plus, Bruker Daltonics) was coupled online with an Agilent 1100 series LC system (Agilent Technologies). 32 Desalted lipids (15 μL in methanol) were loaded onto a 2.0 × 150 mm UK-silica column (Imtakt Corp., Kyoto, Japan) that had been equilibrated with solvent A [chloroform/methanol/50 mM triethylamine−acetate buffer (pH 4.2) (83:16:1, v/v/v)] and were eluted with a 0−100% linear gradient of solvent B [methanol/50 mM triethylamine−acetate buffer (pH 4.2) (3:1, v/v)] for 45 min at a flow rate of 0.1 mL/min. The scan range was 100−2000 m/z.…”

Ganglioside Nanocluster-Targeting Peptidyl Inhibitor Prevents Amyloid β Fibril Formation on the Neuronal Membrane

“…23,24 The fibril-forming capacity is dependent on the oligosaccharide structure of glycosphingolipids (GSLs); for example, GM1-, GD1a-, and GT1b-containing membranes induce the formation of longer fibrils than those containing GD1b and GM2. 23,25 In the present study, we aimed to investigate the inhibition of toxic Aβ assemblies on ganglioside-containing membranes by the ganglioside cluster-binding peptide (GCBP), VWRLLAPPFSNRLLP (Figure 1A). 26 The sequence of GCBP was identified via phage-display selection using a random pentadecapeptide library against the GM1 lipid monolayer.…”

“…Using atomic force microscopy (AFM), we previously showed that free Aβ monomeric molecules are assembled and deposited on ganglioside-enriched reconstituted planar membranes isolated from mouse brains; this finding was later extended to human brains . We termed Aβ assembly-induced nanodomains as Aβ-sensitive ganglioside nanoclusters, which are mimicked by a ganglioside-enriched lipid bilayer composed of synthetic gangliosides, SM, and cholesterol lipids. , The fibril-forming capacity is dependent on the oligosaccharide structure of glycosphingolipids (GSLs); for example, GM1-, GD1a-, and GT1b-containing membranes induce the formation of longer fibrils than those containing GD1b and GM2. , …”