Dataset Information

Cholesterol-rich naked mole-rat brain lipid membranes are susceptible to amyloid beta-induced damage in vitro.

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 (A?) peptide from a young age. Therefore, they represent a particularly favourable organism to study the mechanisms of resistance against A? neurotoxicity. Here we examine the composition, phase behaviour, and A? 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 A? disrupts naked mole-rat brain lipid membranes significantly, breaking the membrane into pieces while mouse brain derived lipids remain largely intact upon A? exposure.

SUBMITTER: Frankel D

PROVIDER: S-EPMC7695401 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Cholesterol-rich naked mole-rat brain lipid membranes are susceptible to amyloid beta-induced damage <i>in vitro</i>.

Frankel Daniel D Davies Matthew M Bhushan Bharat B Kulaberoglu Yavuz Y Urriola-Munoz Paulina P Bertrand-Michel Justine J Pergande Melissa R MR Smith Andrew A AA Preet Swapan S Park Thomas J TJ Vendruscolo Michele M Rankin Kenneth S KS Cologna Stephanie M SM Kumita Janet R JR Cenac Nicolas N St John Smith Ewan E

Aging 20201104 21

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 inter ...[more]

PMID: 33147569

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Project description:BACKGROUND: The naked mole rats (NMRs) are small-sized underground rodents with plenty of unusual traits. Their life expectancy can be up to thirty years, more than seven times longer than laboratory rat. Furthermore, they are resistant to both congenital and experimentally induced cancer genesis. These peculiar physiological and pathological characteristics allow them to become a suitable model for cancer and aging research. RESULTS: In this paper, we carried out a genome-wide comparative analysis of rat and NMR using the recently published genome sequence of NMR. First, we identified all the rat-NMR orthologous genes and specific genes within each of them. The expanded and contracted numbers of protein families in NMR were also analyzed when compared to rat. Seven cancer-related protein families appeared to be significantly expanded, whereas several receptor families were found to be contracted in NMR. We then chose those rat genes that were inexistent in NMR and adopted KEGG pathway database to investigate the metabolic processes in which their proteins may be involved. These genes were significantly enriched in two rat cancer pathways, "Pathway in cancer" and "Bladder cancer". In the rat "Pathway in cancer", 9 out of 14 paths leading to evading apoptosis appeared to be affected in NMR. In addition, a significant number of other NMR-missing genes enriched in several cancer-related pathways have been known to be related to a variety of cancers, implying that many of them may be also related to tumorigenesis in mammals. Finally, investigation of sequence variations among orthologous proteins between rat and NMR revealed that significant fragment insertions/deletions within important functional domains were present in some NMR proteins, which might lead to expressional and/or functional changes of these genes in different species. CONCLUSIONS: Overall, this study provides insights into understanding the possible anti-cancer mechanisms of NMR as well as searching for new cancer-related candidate genes.

Dataset Information

Cholesterol-rich naked mole-rat brain lipid membranes are susceptible to amyloid beta-induced damage in vitro.

Publications

Cholesterol-rich naked mole-rat brain lipid membranes are susceptible to amyloid beta-induced damage <i>in vitro</i>.

Similar Datasets

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