Cholesterol-rich naked mole-rat brain lipid membranes are susceptible to amyloid beta-induced damage in vitro
2020
Urriola-Munoz, Paulina | St John Smith, Ewan | Frankel, Daniel | Davies, Matthew | Bhushan, Bharat | Kulaberoglu, Yavuz | Urriola- Munoz, Paulina | Bertrand-Michel, Justine | Pergande, Melissa, R | Smith, Andrew, A | Preet, Swapan | Park, Thomas, J | Vendruscolo, Michele | Rankin, Kenneth, S | Cologna, Stephanie, M | Kumita, Janet, R | Cenac, Nicolas | St, Ewan | Smith, John | University of Cambridge [UK] (CAM) | Newcastle University [Newcastle] | Institut des Maladies Métaboliques et Cardiovasculaires (I2MC) ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM) | University of Illinois [Chicago] (UIC) ; University of Illinois System | Institut de Recherche en Santé Digestive (IRSD) ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | EPSRC Underpinning Multi-User Equipment Call : EP/P030467/1 | National Science Foundation (NSF) : 1655494 | UIC DFI Fellowship | Cancer Research UK/RCUK : C56829/A22053 | Dunhill Medical Trust : RPGF2002\188 | BBSRC-DTP studentship | Centre for Misfolding Diseases | ANR-18-CE14-0039,LiBacPain,Les lipopeptides produits par le microbiote : de l'hypersensibilité à la thérapie dans le syndrome de l'intestin irritable(2018)
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Show more [+] Less [-]English. Naked mole-rats are extraordinarily long-lived rodents that offer unique opportunities to study the molecular origins of age-related neurodegenerative diseases. Remarkably, they do not accumulate amyloid plaques, even though their brains contain high concentrations of amyloid beta (Aβ) peptide from a young age. Therefore, they represent a particularly favourable organism to study the mechanisms of resistance against Aβ neurotoxicity. Here we examine the composition, phase behaviour, and Aβ interactions of naked mole-rat brain lipids. Relative to mouse, naked mole-rat brain lipids are rich in cholesterol and contain sphingomyelin in lower amounts and of shorter chain lengths. Proteins associated with the metabolism of ceramides, sphingomyelins and sphingosine-1-phosphate receptor 1 were also found to be decreased in naked mole-rat brain lysates. Correspondingly, we find that naked mole-rat brain lipid membranes exhibit a high degree of phase separation, with the liquid ordered phase extending to 80% of the supported lipid bilayer. These observations are consistent with the 'membrane pacemaker' hypothesis of ageing, according to which long-living species have lipid membranes particularly resistant to oxidative damage. We also found that exposure to Aβ disrupts naked mole-rat brain lipid membranes significantly, breaking the membrane into pieces while mouse brain derived lipids remain largely intact upon Aβ exposure.
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