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Department of Pharmacology

 
Author(s): 
Frankel, D, Davies, M, Bhushan, B, Kulaberoglu, Y, Urriola-Munoz, P, Bertrand-Michel, J, Pergande, MR, Smith, AA, Preet, S, Park, TJ, Vendruscolo, M, Rankin, KS, Cologna, SM, Kumita, JR, Cenac, N, St John Smith, E
Abstract: 

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.

Publication ID: 
1243975
Published date: 
4 November 2020
Publication source: 
pubmed
Publication type: 
Journal articles
Journal name: 
Aging (Albany NY)
Publication volume: 
12
Publisher: 
Parent title: 
Edition: 
Publication number: