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Rapamycin regulates cholesterol biosynthesis and cytoplasmic ribosomal proteins in hippocampus and temporal lobe of APP/PS1 mouse.

Abstract：

:As an inhibitor of the immune system and a longevity drug, rapamycin has been suggested as a treatment for Alzheimer's disease, although the underlying mechanisms remain to be clarified. To elucidate the mechanisms, we performed a high-throughput quantitative proteomics analysis and bioinformatics analysis of the changes in the proteome profiles of hippocampus and temporal lobe of wild-type mice, APP/PS1 mice and rapamycin-treated APP/PS1 mice (ProteomeXchange: PXD009540). Morris Water Maze tests were used to evaluate the effectiveness of rapamycin in APP/PS1 treatment and Western blot analysis was used to verify the proteomics data. The results of Morris Water Maze tests indicated that rapamycin improved the spatial learning and memory abilities of APP/PS1 mice. Proteome analysis identified 100 significantly changed (SC) proteins in hippocampus and 260 in temporal lobe in APP/PS1 mice. Among these, 57 proteins in hippocampus and 167 proteins in temporal lobe were rescued by rapamycin. STRING analysis indicated relatively more complicated protein interactions of AD-related rapamycin rescued proteins in temporal lobe. Pathway analysis showed that SC proteins in APP/PS1 mice were mainly enriched in cholesterol biosynthesis pathway and cytoplasmic ribosomal proteins. After rapamycin treatment, the expression of most proteins in these signaling pathways were reversed. Overall, our findings demonstrate that rapamycin may be an potential strategy which can effectively delays the progression of AD.

journal_name

J Neurol Sci

journal_title

Journal of the neurological sciences

authors

Wang X,Xia W,Li K,Zhang Y,Ge W,Ma C

doi

10.1016/j.jns.2019.02.022

subject

Has Abstract

pub_date

2019-04-15 00:00:00

pages

125-139

eissn

0022-510X

issn

1878-5883

pii

S0022-510X(19)30083-8

journal_volume

399

pub_type

杂志文章

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