Matches in SemOpenAlex for { <https://semopenalex.org/work/W4297995606> ?p ?o ?g. }
- W4297995606 endingPage "2220" @default.
- W4297995606 startingPage "2206" @default.
- W4297995606 abstract "A major hallmark of Alzheimer's disease (AD) is the accumulation of extracellular aggregates of amyloid-β (Aβ). Structural polymorphism observed among Aβ fibrils in AD brains seem to correlate with the clinical subtypes suggesting a link between fibril polymorphism and pathology. Since fibrils emerge from a templated growth of low-molecular-weight oligomers, understanding the factors affecting oligomer generation is important. Membrane lipids are key factors to influence early stages of Aβ aggregation and oligomer generation, which cause membrane disruption. We have previously demonstrated that conformationally discrete Aβ oligomers can be generated by modulating the charge, composition, and chain length of lipids and surfactants. Here, we extend our studies into liposomal models by investigating Aβ oligomerization on large unilamellar vesicles (LUVs) of total brain extracts (TBE), reconstituted lipid rafts (LRs), or 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). Varying the vesicle composition by specifically increasing the amount of GM1 gangliosides as a constituent, we found that only GM1-enriched liposomes induce the formation of toxic, low-molecular-weight oligomers. Furthermore, we found that the aggregation on liposome surface and membrane disruption are highly cooperative and sensitive to membrane surface characteristics. Numerical simulations confirm such a cooperativity and reveal that GM1-enriched liposomes form twice as many pores as those formed in the absence GM1. Overall, this study uncovers mechanisms of cooperativity between oligomerization and membrane disruption under controlled lipid compositional bias, and refocuses the significance of the early stages of Aβ aggregation in polymorphism, propagation, and toxicity in AD." @default.
- W4297995606 created "2022-10-01" @default.
- W4297995606 creator A5017991711 @default.
- W4297995606 creator A5058375335 @default.
- W4297995606 creator A5080886331 @default.
- W4297995606 creator A5088198710 @default.
- W4297995606 creator A5088682170 @default.
- W4297995606 date "2022-09-29" @default.
- W4297995606 modified "2023-10-14" @default.
- W4297995606 title "Ganglioside-Enriched Phospholipid Vesicles Induce Cooperative Aβ Oligomerization and Membrane Disruption" @default.
- W4297995606 cites W1016552812 @default.
- W4297995606 cites W1973026127 @default.
- W4297995606 cites W1978416086 @default.
- W4297995606 cites W1982617198 @default.
- W4297995606 cites W1984542598 @default.
- W4297995606 cites W1985889569 @default.
- W4297995606 cites W1988252068 @default.
- W4297995606 cites W1989773342 @default.
- W4297995606 cites W1997822065 @default.
- W4297995606 cites W1999273676 @default.
- W4297995606 cites W2001923760 @default.
- W4297995606 cites W2004098528 @default.
- W4297995606 cites W2007157911 @default.
- W4297995606 cites W2011847302 @default.
- W4297995606 cites W2013650907 @default.
- W4297995606 cites W2013780997 @default.
- W4297995606 cites W2022756726 @default.
- W4297995606 cites W2024996842 @default.
- W4297995606 cites W2026714067 @default.
- W4297995606 cites W2030325989 @default.
- W4297995606 cites W2033382511 @default.
- W4297995606 cites W2036697342 @default.
- W4297995606 cites W2037934043 @default.
- W4297995606 cites W2038086035 @default.
- W4297995606 cites W2038980320 @default.
- W4297995606 cites W2047108386 @default.
- W4297995606 cites W2053665966 @default.
- W4297995606 cites W2054086227 @default.
- W4297995606 cites W2060914703 @default.
- W4297995606 cites W2062102053 @default.
- W4297995606 cites W2064651437 @default.
- W4297995606 cites W2067464601 @default.
- W4297995606 cites W2074619433 @default.
- W4297995606 cites W2076544353 @default.
- W4297995606 cites W2078450707 @default.
- W4297995606 cites W2081855136 @default.
- W4297995606 cites W2083258595 @default.
- W4297995606 cites W2084792706 @default.
- W4297995606 cites W2085538443 @default.
- W4297995606 cites W2089843826 @default.
- W4297995606 cites W2099077346 @default.
- W4297995606 cites W2110060346 @default.
- W4297995606 cites W2112735281 @default.
- W4297995606 cites W2121977115 @default.
- W4297995606 cites W2125989811 @default.
- W4297995606 cites W2134843571 @default.
- W4297995606 cites W2135701488 @default.
- W4297995606 cites W2150999725 @default.
- W4297995606 cites W2158535880 @default.
- W4297995606 cites W2162741488 @default.
- W4297995606 cites W2168648059 @default.
- W4297995606 cites W2208459292 @default.
- W4297995606 cites W2212272536 @default.
- W4297995606 cites W2231120016 @default.
- W4297995606 cites W2314355563 @default.
- W4297995606 cites W2328915352 @default.
- W4297995606 cites W2332428172 @default.
- W4297995606 cites W2407203842 @default.
- W4297995606 cites W2408969117 @default.
- W4297995606 cites W2508053418 @default.
- W4297995606 cites W2571390534 @default.
- W4297995606 cites W2575438441 @default.
- W4297995606 cites W2580174306 @default.
- W4297995606 cites W2583728075 @default.
- W4297995606 cites W2742420766 @default.
- W4297995606 cites W2750851336 @default.
- W4297995606 cites W2753638558 @default.
- W4297995606 cites W2755454576 @default.
- W4297995606 cites W2783923368 @default.
- W4297995606 cites W2786777202 @default.
- W4297995606 cites W2791381827 @default.
- W4297995606 cites W2799392762 @default.
- W4297995606 cites W2800189263 @default.
- W4297995606 cites W2802733986 @default.
- W4297995606 cites W2897670905 @default.
- W4297995606 cites W2972561671 @default.
- W4297995606 cites W3009098505 @default.
- W4297995606 cites W3010695687 @default.
- W4297995606 cites W3038168026 @default.
- W4297995606 cites W3047111108 @default.
- W4297995606 cites W3048183351 @default.
- W4297995606 cites W3114147866 @default.
- W4297995606 cites W3121140739 @default.
- W4297995606 cites W3194046247 @default.
- W4297995606 cites W3206570944 @default.
- W4297995606 cites W377222851 @default.
- W4297995606 doi "https://doi.org/10.1021/acs.biochem.2c00495" @default.
- W4297995606 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36173882" @default.